Transforming Growth Factor-β Pathway: Biological Functions and Therapeutic Targets

Reham Hassan Mekky , Mohammed E. Abo-El Fetoh , Safaa A. Faheem , Abdullah F. Radwan , Mariam H. Fawzy , Aya M. Mustafa , Mohamed A. Said , Daniela Calina , Javad Sharifi-Rad , William C. Cho

MedComm ›› 2025, Vol. 6 ›› Issue (7) : e70278

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MedComm ›› 2025, Vol. 6 ›› Issue (7) : e70278 DOI: 10.1002/mco2.70278
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Transforming Growth Factor-β Pathway: Biological Functions and Therapeutic Targets

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Abstract

Cancer progression is often driven by aberrant cell growth and genetic mutations, leading to metastasis. The transforming growth factor-beta (TGF-β) pathway, a key regulator of cellular growth and differentiation, exhibits dual roles in cancer by initially acting as a tumor suppressor and later promoting tumor progression and metastasis. Natural compounds, recognized for their diverse bioactivities and low toxicity, have shown potential in targeting cancer-related pathways, including TGF-β signaling. This review examines the therapeutic potential of natural products in modulating TGF-β signaling and their anticancer effects across various cancer types. We evaluated relevant preclinical and clinical studies assessing the impact of natural products on TGF-β modulation and cancer progression. Natural compounds from sources such as plants impact TGF-β signaling, influencing processes like cell proliferation, apoptosis, and angiogenesis. Key compounds reviewed include ginsenosides, halofuginone, and epigallocatechin gallate, demonstrating significant anticancer activity via TGF-β pathway modulation. These findings suggest natural products may serve as complementary therapies in cancer treatment by targeting TGF-β signaling, potentially improving patient outcomes. Continued research and clinical evaluation are necessary to integrate these compounds into conventional cancer therapies, aiming to offer safer, cost-effective options that enhance quality of life.

Keywords

angiogenesis / apoptosis / cancer progression / natural compounds / TGF-β pathway / therapeutic modulation

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Reham Hassan Mekky, Mohammed E. Abo-El Fetoh, Safaa A. Faheem, Abdullah F. Radwan, Mariam H. Fawzy, Aya M. Mustafa, Mohamed A. Said, Daniela Calina, Javad Sharifi-Rad, William C. Cho. Transforming Growth Factor-β Pathway: Biological Functions and Therapeutic Targets. MedComm, 2025, 6(7): e70278 DOI:10.1002/mco2.70278

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References

[1]

G. E. Chaudhry, A. Md Akim, Y. Y. Sung, and T. M. T. Sifzizul, “Cancer and Apoptosis: The Apoptotic Activity of Plant and Marine Natural Products and Their Potential as Targeted Cancer Therapeutics,” Frontiers in Pharmacology 13 (2022): 842376.

[2]

P. Costa, S. L. A. Sales, D. P. Pinheiro, et al., “Epigenetic Reprogramming in Cancer: From Diagnosis to Treatment,” Frontiers in Cell and Developmental Biology 11 (2023): 1116805.

[3]

A. R. da Cunha, K. Compton, R. X. Xu, et al., “The Global, Regional, and National Burden of Adult Lip, Oral, and Pharyngeal Cancer in 204 Countries and Territories a Systematic Analysis for the Global Burden of Disease Study 2019,” Jama Oncology 9, no. 10 (2023): 1401-1416.

[4]

B. Liu, H. Zhou, L. Tan, K. T. H. Siu, X. Y. Guan, “Exploring Treatment Options in Cancer: Tumor Treatment Strategies,” Signal Transduction and Targeted Therapy 9, no. 1 (2024): 175, https://doi.org/10.1038/s41392-024-01856-7.

[5]

U. Anand, A. Dey, A. K. S. Chandel, et al., “Cancer Chemotherapy and Beyond: Current Status, Drug Candidates, Associated Risks and Progress in Targeted Therapeutics,” Genes & Diseases 10, no. 4 (2023): 1367-1401.

[6]

M. Ammad, Z. Javed, H. Sadia, et al., “Advancements in Long Non-coding RNA-based Therapies for Cancer: Targeting, Delivery, and Clinical Implications,” Medical Oncology 41, no. 11 (2024): 292.

[7]

D. C. Attri, P. Dhyani, V. L. Trivedi, et al., “Current Evidence on Molecular Mechanisms of Andrographolide in Cancer,” Current Medicinal Chemistry (2024).

[8]

R. Bala, R. Madaan, S. Chauhan, et al., “Revitalizing allicin for Cancer Therapy: Advances in Formulation Strategies to Enhance Bioavailability, Stability, and Clinical Efficacy,” Naunyn-Schmiedeberg's Archives of Pharmacology 397, no. 2 (2024): 703-724.

[9]

E. Batlle and J. Massagué, “Transforming Growth Factor-β Signaling in Immunity and Cancer,” Immunity 50, no. 4 (2019): 924-940.

[10]

S. Liu, J. Ren, and P. Ten Dijke, “Targeting TGFβ Signal Transduction for Cancer Therapy,” Signal Transduction and Targeted Therapy 6, no. 1 (2021): 8.

[11]

A. B. Baba, B. Rah, G. R. Bhat, et al., “Transforming Growth Factor-Beta (TGF-β) Signaling in Cancer-A Betrayal within,” Frontiers in Pharmacology 13 (2022): 791272.

[12]

T. Matsuoka and M. Yashiro, “The Role of the Transforming Growth Factor-β Signaling Pathway in Gastrointestinal Cancers,” Biomolecules 13, no. 10 (2023): 1551.

[13]

N. A. Kuburich, T. Sabapathy, B. R. Demestichas, J. J. Maddela, den P. Hollander, and S. A. Mani, “Proactive and Reactive Roles of TGF-β in Cancer,” Seminars in Cancer Biology 95 (2023): 120-139.

[14]

R. Ge and G. M. Huang, “Targeting Transforming Growth Factor Beta Signaling in Metastatic Osteosarcoma,” Journal of Bone Oncology 43 (2023): 100513.

[15]

R. Derynck, S. J. Turley, and R. J. Akhurst, “TGFβ Biology in Cancer Progression and Immunotherapy,” Nature Reviews Clinical Oncology 18, no. 1 (2021): 9-34.

[16]

Y. Zhang, L. Zhou, G. Cheng, et al., “Cordyceps sinensis Ameliorates Idiopathic Pulmonary Fibrosis in Mice via Inhibiting Mitochondrion-mediated Oxidative Stress,” MedComm - Future Medicine 3, no. 3 (2024): e91.

[17]

P. J. Sime, Z. Xing, F. L. Graham, K. G. Csaky, and J. Gauldie, “Adenovector-mediated Gene Transfer of Active Transforming Growth Factor-beta1 Induces Prolonged Severe Fibrosis in Rat Lung,” Journal of Clinical Investigation 100, no. 4 (1997): 768-776.

[18]

N. Inui, S. Sakai, and M. Kitagawa, “Molecular Pathogenesis of Pulmonary Fibrosis, With Focus on Pathways Related to TGF-β and the Ubiquitin-Proteasome Pathway,” International Journal of Molecular Sciences 22, no. 11 (2021): 6107.

[19]

D. Xiang, J. Zou, X. Zhu, et al., “Physalin D Attenuates Hepatic Stellate Cell Activation and Liver Fibrosis by Blocking TGF-β/Smad and YAP Signaling,” Phytomedicine 78 (2020): 153294.

[20]

Y. Isaka, “Targeting TGF-β Signaling in Kidney Fibrosis,” International Journal of Molecular Sciences 19, no. 9 (2018): 2532.

[21]

H. Khalil, O. Kanisicak, V. Prasad, et al., “Fibroblast-specific TGF-β-Smad2/3 Signaling Underlies Cardiac Fibrosis,” Journal of Clinical Investigation 127, no. 10 (2017): 3770-3783.

[22]

L. Sun, M. Xiu, S. Wang, et al., “Lipopolysaccharide Enhances TGF-β1 Signalling Pathway and Rat Pancreatic Fibrosis,” Journal of Cellular and Molecular Medicine 22, no. 4 (2018): 2346-2356.

[23]

H. Lin, B. Dong, L. Qi, et al., “Inhibitory Smads Suppress Pancreatic Stellate Cell Activation Through Negative Feedback in Chronic Pancreatitis,” Annals of Translational Medicine 9, no. 5 (2021): 384.

[24]

M. Shou, H. Zhou, and L. Ma, “New Advances in Cancer Therapy Targeting TGF-β Signaling Pathways,” Molecular Therapy Oncology 31 (2023): 100755.

[25]

B.-G. Kim, E. Malek, S. H. Choi, J. J. Ignatz-Hoover, and J. J. Driscoll, “Novel Therapies Emerging in Oncology to Target the TGF-β Pathway,” Journal of Hematology & Oncology 14 (2021): 1-20.

[26]

S. Liu, A. R. Khan, X. Yang, B. Dong, J. Ji, and G. Zhai, “The Reversal of Chemotherapy-induced Multidrug Resistance by Nanomedicine for Cancer Therapy,” Journal of Controlled Release 335 (2021): 1-20.

[27]

F. Gsottberger, C. Meier, A. Ammon, et al., “Targeted Inhibition of Protein Synthesis Renders Cancer Cells Vulnerable to Apoptosis by Unfolded Protein Response,” Cell Death & Disease 14, no. 8 (2023): 561.

[28]

Y. Guo, M. Ashrafizadeh, M. M. Tambuwala, J. Ren, G. Orive, and G. Yu, “P-glycoprotein (P-gp)-driven Cancer Drug Resistance: Biological Profile, Non-coding RNAs, Drugs and Nanomodulators,” Drug Discovery Today 29, no. 11 (2024): 104161.

[29]

K. Gach-Janczak, J. Drogosz-Stachowicz, A. Janecka, K. Wtorek, and M. Mirowski, “Historical Perspective and Current Trends in Anticancer Drug Development,” Cancers (Basel) 16, no. 10 (2024): 1878.

[30]

A. L. Parker, M. Benguigui, J. Fornetti, et al., “Current Challenges in Metastasis Research and Future Innovation for Clinical Translation,” Clinical & Experimental Metastasis 39, no. 2 (2022): 263-277.

[31]

A. Naeem, P. Hu, M. Yang, et al., “Natural Products as Anticancer Agents: Current Status and Future Perspectives,” Molecules (Basel, Switzerland) 27, no. 23 (2022): 8367.

[32]

F. C. Cadoná, R. F. Dantas, G. H. de Mello, and F. P. Silva, “Natural Products Targeting Into Cancer Hallmarks: An Update on Caffeine, Theobromine, and (+)-catechin,” Critical Reviews in Food Science and Nutrition 62, no. 26 (2022): 7222-7241.

[33]

P. Chunarkar-Patil, M. Kaleem, R. Mishra, et al., “Anticancer Drug Discovery Based on Natural Products: From Computational Approaches to Clinical Studies,” Biomedicines 12, no. 1 (2024): 201.

[34]

S. Motyka, K. Jafernik, H. Ekiert, et al., “Podophyllotoxin and Its Derivatives: Potential Anticancer Agents of Natural Origin in Cancer Chemotherapy,” Biomedicine & Pharmacotherapy 158 (2023): 114145.

[35]

D. Kitic, B. Miladinovic, M. Randjelovic, et al., “Anticancer and Chemopreventive Potential of Morinda Citrifolia L. bioactive Compounds: A Comprehensive Update,” Phytotherapy Research 38, no. 4 (2024): 1932-1950.

[36]

L. Hardt, Y. Mahamat-Saleh, D. Aune, and S. Schlesinger, “Plant-Based Diets and Cancer Prognosis: A Review of Recent Research,” Current Nutrition Reports 11, no. 4 (2022): 695-716.

[37]

M. L. Coêlho, M. T. Islam, G. Laylson da Silva Oliveira, et al., “Cytotoxic and Antioxidant Properties of Natural Bioactive Monoterpenes Nerol, Estragole, and 3,7-Dimethyl-1-Octanol,” Advances in Pharmacological and Pharmaceutical Sciences 2022 (2022): 8002766-8002766.

[38]

R. Hossain, P. Ray, C. Sarkar, et al., “Natural Compounds or Their Derivatives Against Breast Cancer: A Computational Study,” BioMed Research International 2022 (2022): 5886269-5886269.

[39]

G. Peron, A. Mastinu, S. I. Peña-Corona, et al., “Silvestrol, a Potent Anticancer Agent With Unfavourable Pharmacokinetics: Current Knowledge on Its Pharmacological Properties and Future Directions for the Development of Novel Drugs,” Biomedicine & Pharmacotherapy 177 (2024): 117047.

[40]

M. Kamle, S. Pandhi, S. Mishra, et al., “Camptothecin and Its Derivatives: Advancements, Mechanisms and Clinical Potential in Cancer Therapy,” Medical Oncology 41, no. 11 (2024): 263.

[41]

K. A. Mansour, A. Elbermawi, A. A. Al-Karmalawy, M. F. Lahloub, and M. El-Neketi, “Cytotoxic Effects of Extracts Obtained From Plants of the Oleaceae family: Bio-guided Isolation and Molecular Docking of New Secoiridoids From Jasminum Humile,” Pharmaceutical Biology 60, no. 1 (2022): 1374-1383.

[42]

Z. Javed, K. Khan, J. Herrera-Bravo, et al., “Myricetin: Targeting Signaling Networks in Cancer and Its Implication in Chemotherapy,” Cancer Cell International 22, no. 1 (2022): 239.

[43]

D. Liu, A. P. van der Zalm, J. Koster, et al., “Predictive Biomarkers for Response to TGF- β Inhibition in Resensitizing Chemo(radiated) Esophageal Adenocarcinoma,” Pharmacological Research 207 (2024): 107315.

[44]

M. H. Barcellos-Hoff and J. L. Gulley, “Molecular Pathways and Mechanisms of TGFβ in Cancer Therapy,” Clinical Cancer Research 29, no. 11 (2023): 2025-2033.

[45]

R. Derynck, S. J. Turley, and R. J. Akhurst, “TGFbeta Biology in Cancer Progression and Immunotherapy,” Nature Reviews Clinical Oncology 18, no. 1 (2021): 9-34.

[46]

M. Turati, A. Mousset, N. Issa, A. Turtoi, and R. Ronca, “TGF-β Mediated Drug Resistance in Solid Cancer,” Cytokine & Growth Factor Reviews 71-72 (2023): 54-65.

[47]

A. Gazzillo, M. A. Polidoro, C. Soldani, B. Franceschini, A. Lleo, and M. Donadon, “Relationship Between Epithelial-to-Mesenchymal Transition and Tumor-Associated Macrophages in Colorectal Liver Metastases,” International Journal of Molecular Sciences 23, no. 24 (2022): 16197.

[48]

A. O. Giarratana, C. M. Prendergast, M. M. Salvatore, and K. M. Capaccione, “TGF-β Signaling: Critical Nexus of Fibrogenesis and Cancer,” Journal of Translational Medicine 22, no. 1 (2024): 594.

[49]

Z. Deng, T. Fan, C. Xiao, et al., “TGF-β Signaling in Health, Disease, and Therapeutics,” Signal Transduction and Targeted Therapy 9, no. 1 (2024): 61.

[50]

Y. Yang, W. L. Ye, R. N. Zhang, et al., “The Role of TGF-beta Signaling Pathways in Cancer and Its Potential as a Therapeutic Target,” Evidence-Based Complementary and Alternative Medicine 2021 (2021): 6675208.

[51]

M. Abbastabar, M. Kheyrollah, K. Azizian, et al., “Multiple Functions of p27 in Cell Cycle, Apoptosis, Epigenetic Modification and Transcriptional Regulation for the Control of Cell Growth: A Double-edged Sword Protein,” Dna Repair 69 (2018): 63-72.

[52]

C. Petritsch, H. Beug, A. Balmain, and M. Oft, “TGF-beta Inhibits p70 S6 Kinase via Protein Phosphatase 2A to Induce G(1) Arrest,” Genes & Development 14, no. 24 (2000): 3093-3101.

[53]

Q. Wang, F. Xiong, G. Wu, et al., “SMAD Proteins in TGF-β Signalling Pathway in Cancer: Regulatory Mechanisms and Clinical Applications,” Diagnostics (Basel) 13, no. 17 (2023): 2769.

[54]

A. Glaviano, A. S. C. Foo, H. Y. Lam, et al., “PI3K/AKT/mTOR Signaling Transduction Pathway and Targeted Therapies in Cancer,” Molecular Cancer 22, no. 1 (2023): 138.

[55]

M. Kammoun, J. Piquereau, L. Nadal-Desbarats, et al., “Novel Role of Tieg1 in Muscle Metabolism and Mitochondrial Oxidative Capacities,” Acta Physiologica (Oxford) 228, no. 3 (2020): e13394.

[56]

A. B. Baba, B. Rah, G. R. Bhat, et al., “Transforming Growth Factor-Beta (TGF-beta) Signaling in Cancer-A Betrayal within,” Frontiers in Pharmacology 13 (2022): 791272.

[57]

M. Zhao, L. Mishra, and C. X. Deng, “The Role of TGF-β/SMAD4 Signaling in Cancer,” International Journal of Biological Sciences 14, no. 2 (2018): 111-123.

[58]

J. Dardare, A. Witz, J. L. Merlin, P. Gilson, and A. Harlé, “SMAD4 and the TGFβ Pathway in Patients With Pancreatic Ductal Adenocarcinoma,” International Journal of Molecular Sciences 21, no. 10 (2020): 3534.

[59]

V. W. Xue, J. Y. Chung, C. A. G. Cordoba, et al., “Transforming Growth Factor-beta: A Multifunctional Regulator of Cancer Immunity,” Cancers (Basel) 12, no. 11 (2020): 3099.

[60]

B. G. Kim, E. Malek, S. H. Choi, J. J. Ignatz-Hoover, and J. J. Driscoll, “Novel Therapies Emerging in Oncology to Target the TGF-beta Pathway,” Journal of Hematology & Oncology 14, no. 1 (2021): 55.

[61]

R. Vogelmann, M. D. Nguyen-Tat, K. Giehl, G. Adler, D. Wedlich, and A Menke. TGFbeta-induced Downregulation of E-cadherin-based Cell-cell Adhesion Depends on PI3-kinase and PTEN. Journal of Cell Science 2005; 118(Pt 20): 4901-4912.

[62]

Q. Zhang, B. T. Helfand, T. L. Jang, et al. Nuclear Factor-kappaB-mediated Transforming Growth Factor-beta-induced Expression of vimentin Is an Independent Predictor of Biochemical Recurrence After Radical Prostatectomy. Clinical Cancer Research 2009; 15(10): 3557-3567.

[63]

Y. Wu, X. Zhang, M. Salmon, X. Lin, and Z. E. Zehner, “TGFbeta1 regulation of Vimentin Gene Expression During Differentiation of the C2C12 Skeletal Myogenic Cell Line Requires Smads, AP-1 and Sp1 family Members,” Biochimica Et Biophysica Acta 1773, no. 3 (2007): 427-439.

[64]

J. Xu, S. Lamouille, and R. Derynck, “TGF-beta-induced Epithelial to Mesenchymal Transition,” Cell Research 19, no. 2 (2009): 156-172.

[65]

M. Adorno, M. Cordenonsi, M. Montagner, et al., “A Mutant-p53/Smad Complex Opposes p63 to Empower TGFbeta-induced Metastasis,” Cell 137, no. 1 (2009): 87-98.

[66]

T. Shimo, T. Nakanishi, T. Nishida, et al., “Involvement of CTGF, a Hypertrophic Chondrocyte-specific Gene Product, in Tumor Angiogenesis,” Oncology 61, no. 4 (2001): 315-322.

[67]

J. Wang, Y. Wang, Y. Wang, Y. Ma, Y. Lan, and X. Yang, “Transforming Growth Factor Beta-regulated microRNA-29a Promotes Angiogenesis Through Targeting the Phosphatase and Tensin Homolog in Endothelium,” Journal of Biological Chemistry 288, no. 15 (2013): 10418-10426.

[68]

A. Safina, E. Vandette, and A. V. Bakin, “ALK5 promotes Tumor Angiogenesis by Upregulating Matrix Metalloproteinase-9 in Tumor Cells,” Oncogene 26, no. 17 (2007): 2407-2422.

[69]

E. Vivier, E. Tomasello, M. Baratin, T. Walzer, and S. Ugolini, “Functions of Natural Killer Cells,” Nature Immunology 9, no. 5 (2008): 503-510.

[70]

S. Regis, A. Dondero, F. Caliendo, C. Bottino, and R. Castriconi, “NK Cell Function Regulation by TGF-beta-Induced Epigenetic Mechanisms,” Frontiers in Immunology 11 (2020): 311.

[71]

Z. Li, D. Li, A. Tsun, and B. Li, “FOXP3+ regulatory T Cells and Their Functional Regulation,” Cellular & Molecular Immunology 12, no. 5 (2015): 558-565.

[72]

M. Gachpazan, H. Kashani, S. M. Hassanian, et al., “Therapeutic Potential of Targeting Transforming Growth Factor-beta in Colorectal Cancer: Rational and Progress,” Current Pharmaceutical Design 25, no. 38 (2019): 4085-4089.

[73]

J. Y. Son, S. Y. Park, S. J. Kim, et al., “EW-7197, a Novel ALK-5 Kinase Inhibitor, Potently Inhibits Breast to Lung Metastasis,” Molecular Cancer Therapeutics 13, no. 7 (2014): 1704-1716.

[74]

S. Herbertz, J. S. Sawyer, A. J. Stauber, et al., “Clinical Development of galunisertib (LY2157299 monohydrate), a Small Molecule Inhibitor of Transforming Growth Factor-beta Signaling Pathway,” Drug Design, Development and Therapy 9 (2015): 4479-4499.

[75]

Y. Tie, F. Tang, D. Peng, Y. Zhang, and H. Shi, “TGF-beta Signal Transduction: Biology, Function and Therapy for Diseases,” Molecular Biomed 3, no. 1 (2022): 45.

[76]

M. S. Gordon, R. Ilaria, D. P. de Alwis, et al., “A Phase I Study of Tasisulam Sodium (LY573636 sodium), a Novel Anticancer Compound, Administered as a 24-h Continuous Infusion in Patients With Advanced Solid Tumors,” Cancer Chemotheraphy and Pharmacology 71, no. 1 (2013): 21-27.

[77]

M. Tojo, Y. Hamashima, A. Hanyu, et al., “The ALK-5 Inhibitor A-83-01 Inhibits Smad Signaling and Epithelial-to-mesenchymal Transition by Transforming Growth Factor-beta,” Cancer Science 96, no. 11 (2005): 791-800.

[78]

S. Matsuyama, M. Iwadate, M. Kondo, et al., “SB-431542 and Gleevec Inhibit Transforming Growth Factor-beta-induced Proliferation of human Osteosarcoma Cells,” Cancer Research 63, no. 22 (2003): 7791-7798.

[79]

C. J. Martin, A. Datta, C. Littlefield, et al., “Selective Inhibition of TGFbeta1 Activation Overcomes Primary Resistance to Checkpoint Blockade Therapy by Altering Tumor Immune Landscape,” Science Translational Medicine 12, no. 536 (2020): eaay8456.

[80]

J. C. Morris, A. R. Tan, T. E. Olencki, et al., “Phase I Study of GC1008 (fresolimumab): A human Anti-transforming Growth Factor-beta (TGFbeta) Monoclonal Antibody in Patients With Advanced Malignant Melanoma or Renal Cell Carcinoma,” PLoS ONE 9, no. 3 (2014): e90353.

[81]

A. W. Tolcher, J. D. Berlin, J. Cosaert, et al., “A Phase 1 Study of Anti-TGFbeta Receptor Type-II Monoclonal Antibody LY3022859 in Patients With Advanced Solid Tumors,” Cancer Chemotheraphy and Pharmacology 79, no. 4 (2017): 673-680.

[82]

K. M. Moore, G. J. Thomas, S. W. Duffy, et al., “Therapeutic Targeting of Integrin alphavbeta6 in Breast Cancer,” JNCI: Journal of the National Cancer Institute 106, no. 8 (2014): dju169.

[83]

A. Bandyopadhyay, F. Lopez-Casillas, S. N. Malik, et al., “Antitumor Activity of a Recombinant Soluble Betaglycan in human Breast Cancer Xenograft,” Cancer Research 62, no. 16 (2002): 4690-4695.

[84]

P. Fenaux, U. Platzbecker, G. J. Mufti, et al., “Luspatercept in Patients With Lower-Risk Myelodysplastic Syndromes,” New England Journal of Medicine 382, no. 2 (2020): 140-151.

[85]

M. E. Gleave and B. P. Monia, “Antisense Therapy for Cancer,” Nature Reviews Cancer 5, no. 6 (2005): 468-479.

[86]

K. H. Schlingensiepen, R. Schlingensiepen, A. Steinbrecher, et al., “Targeted Tumor Therapy With the TGF-beta 2 Antisense Compound AP 12009,” Cytokine & Growth Factor Reviews 17, no. 1-2 (2006): 129-139.

[87]

F. Jaschinski, T. Rothhammer, P. Jachimczak, C. Seitz, A. Schneider, and K. H. Schlingensiepen, “The Antisense Oligonucleotide Trabedersen (AP 12009) for the Targeted Inhibition of TGF-beta2,” Current Pharmaceutical Biotechnology 12, no. 12 (2011): 2203-2213.

[88]

P. Lampropoulos, A. Zizi-Sermpetzoglou, S. Rizos, A. Kostakis, N. Nikiteas, and A. G. Papavassiliou, “TGF-beta Signalling in Colon Carcinogenesis,” Cancer Letters 314, no. 1 (2012): 1-7.

[89]

P. Hau, P. Jachimczak, and U. Bogdahn, “Treatment of Malignant Gliomas With TGF-beta2 Antisense Oligonucleotides,” Expert Review of Anticancer Therapy 9, no. 11 (2009): 1663-1674.

[90]

S. Khatua, S. Nandi, A. Nag, et al., “Homoharringtonine: Updated Insights Into Its Efficacy in Hematological Malignancies, Diverse Cancers and Other Biomedical Applications,” European Journal of Medical Research 29, no. 1 (2024): 269.

[91]

J. Chen, Q. Mu, X. Li, et al., “Homoharringtonine Targets Smad3 and TGF-β Pathway to Inhibit the Proliferation of Acute Myeloid Leukemia Cells,” Oncotarget 8, no. 25 (2017): 40318-40326.

[92]

B. Li, J. Zhao, C. Z. Wang, et al., “Ginsenoside Rh2 Induces Apoptosis and Paraptosis-Like Cell Death in Colorectal Cancer Cells Through Activation of p53,” Cancer Letters 301, no. 2 (2011): 185-192.

[93]

Q. R. Hu, Y. Pan, H. C. Wu, et al., “The Ways for Ginsenoside Rh2 to Fight Against Cancer: The Molecular Evidences in Vitro and in Vivo,” Journal of Ginseng Research 47, no. 2 (2023): 173-182.

[94]

D. Wang, M. Tian, Y. Fu, et al., “Halofuginone Inhibits Tumor Migration and Invasion by Affecting Cancer-associated Fibroblasts in Oral Squamous Cell Carcinoma. Original Research,” Frontiers in Pharmacology 13 (2022): 1056337.

[95]

P. A. Assis, L. L. De Figueiredo-Pontes, A. S. G. Lima, et al., “Halofuginone Inhibits Phosphorylation of SMAD-2 Reducing Angiogenesis and Leukemia Burden in an Acute Promyelocytic Leukemia Mouse Model,” Journal of Experimental & Clinical Cancer Research 34, no. 1 (2015): 65.

[96]

L. L. de Figueiredo-Pontes, P. A. Assis, B. A. A. Santana-Lemos, et al., “Halofuginone Has Anti-Proliferative Effects in Acute Promyelocytic Leukemia by Modulating the Transforming Growth Factor Beta Signaling Pathway,” PLoS ONE 6, no. 10 (2011): e26713.

[97]

M. Satoh, Y. Takemura, H. Hamada, Y. Sekido, and S. Kubota, “EGCG Induces human Mesothelioma Cell Death by Inducing Reactive Oxygen Species and Autophagy,” Cancer Cell International 13, no. 1 (2013): 19.

[98]

B. Goker, C. Caliskan, H. Onur Caglar, et al., “Synergistic Effect of Ponatinib and Epigallocatechin-3-gallate Induces Apoptosis in Chronic Myeloid Leukemia Cells Through Altering Expressions of Cell Cycle Regulatory Genes,” Journal of B.U.ON 19, no. 4 (2014): 992-998.

[99]

L. Zhao, S. Liu, X. Che, et al., “Bufalin Inhibits TGF-β-induced Epithelial-to-mesenchymal Transition and Migration in human Lung Cancer A549 Cells by Downregulating TGF-β Receptors,” International Journal of Molecular Medicine 36, no. 3 (2015): 645-652.

[100]

K.-S. Chung, S.-H. Cho, J.-S. Shin, et al., “Ginsenoside Rh2 Induces Cell Cycle Arrest and Differentiation in human Leukemia Cells by Upregulating TGF-β Expression,” Carcinogenesis 34, no. 2 (2012): 331-340.

[101]

L. Shen, L.-L. Zhang, H. Li, et al., “Oroxylin A Inhibits the Generation of Tregs in Non-small Cell Lung Cancer,” Oncotarget 8, no. 30 (2017): 49395.

[102]

Z. Faisal, A. Mazhar, S. A. Batool, et al., “Exploring the Multimodal Health-promoting Properties of resveratrol: A Comprehensive Review,” Food Science & Nutrition 12, no. 4 (2024): 2240-2258.

[103]

H. Wang, H. Zhang, L. Tang, et al., “Resveratrol Inhibits TGF-β1-induced Epithelial-to-mesenchymal Transition and Suppresses Lung Cancer Invasion and Metastasis,” Toxicology 303 (2013): 139-146.

[104]

G. Han, Y. Wang, T. Liu, et al., “Salvianolic Acid B Acts Against Non‑Small Cell Lung Cancer A549 Cells via Inactivation of the MAPK and Smad2/3 Signaling Pathways,” Molecular Medicine Reports 25, no. 5 (2022): 1-11.

[105]

F. Hai-Tao, Z. Wen-Wen, L. Jin-Jian, W. Yi-Tao, and C. Xiu-Ping, “Hypaconitine Inhibits TGF-β1-induced Epithelial-mesenchymal Transition and Suppresses Adhesion, Migration, and Invasion of Lung Cancer A549 Cells,” Chinese Journal of Natural Medicines 15, no. 6 (2017): 427-435.

[106]

E. Jo, S. J. Park, Y. S. Choi, W.-K. Jeon, and B.-C. Kim, “Kaempferol Suppresses Transforming Growth Factor-β1-induced Epithelial-to-mesenchymal Transition and Migration of A549 Lung Cancer Cells by Inhibiting Akt1-mediated Phosphorylation of Smad3 at Threonine-179,” Neoplasia 17, no. 7 (2015): 525-537.

[107]

J. S. Ruan, H. Zhou, L. Yang, et al., “Ursolic Acid Attenuates TGF-β1-Induced Epithelial-Mesenchymal Transition in NSCLC by Targeting Integrin αVβ5/MMPs Signaling,” Oncology Research 27, no. 5 (2019): 593.

[108]

S. Dai, C. Wang, X. Zhao, et al., “Cucurbitacin B: A Review of Its Pharmacology, Toxicity, and Pharmacokinetics,” Pharmacological Research 187 (2023): 106587.

[109]

R. Yuan, Q. Fan, X. Liang, et al., “Cucurbitacin B Inhibits TGF-β1-induced Epithelial-mesenchymal Transition (EMT) in NSCLC Through Regulating ROS and PI3K/Akt/mTOR Pathways,” Chinese Medicine 17, no. 1 (2022): 24.

[110]

G. De Rubis, K. R. Paudel, G. Liu, et al., “Berberine-loaded Engineered Nanoparticles Attenuate TGF-β-induced Remodelling in human Bronchial Epithelial Cells,” Toxicology in Vitro 92 (2023): 105660.

[111]

R. Hossain, C. Quispe, J. Herrera-Bravo, et al., “Neurobiological Promises of the Bitter Diterpene Lactone Andrographolide,” Oxidative Medicine and Cellular Longevity 2022 (2022): 3079577.

[112]

H.-H. Lin, C.-W. Tsai, F.-P. Chou, et al., “Andrographolide Down-regulates Hypoxia-inducible Factor-1α in human Non-small Cell Lung Cancer A549 Cells,” Toxicology and Applied Pharmacology 250, no. 3 (2011): 336-345.

[113]

C. Da, Y. Liu, Y. Zhan, K. Liu, and R. Wang, “Nobiletin Inhibits Epithelial-mesenchymal Transition of human Non-small Cell Lung Cancer Cells by Antagonizing the TGF-β1/Smad3 Signaling Pathway,” Oncology Reports 35, no. 5 (2016): 2767-2774.

[114]

P. C. Zhong, Z. W. Liu, Q. C. Xing, J. Chen, and R. P. Yang, “Neferine Inhibits the Development of Lung Cancer Cells by Downregulating TGF-β to Regulate MST1/ROS-induced Pyroptosis,” The Kaohsiung Journal of Medical Sciences 39, no. 11 (2023): 1106-1118.

[115]

M.-W. Byun, “Schizonepeta tenuifolia Ethanol Extract Exerts Anti-inflammatory Activity Through the Inhibition of TLR4 Signaling in Lipopolysaccharide-stimulated Macrophage Cells,” Journal of Medicinal Food 17, no. 3 (2014): 350-356.

[116]

J. Li, Y. Cheng, W. Qu, et al., “Fisetin, a Dietary Flavonoid, Induces Cell Cycle Arrest and Apoptosis Through Activation of p53 and Inhibition of NF-kappa B Pathways in Bladder Cancer Cells,” Basic & Clinical Pharmacology & Toxicology 108, no. 2 (2011): 84-93.

[117]

X.-F. Liu, H.-J. Long, X.-Y. Miao, G.-L. Liu, and H.-L. Yao, “Fisetin Inhibits Liver Cancer Growth in a Mouse Model: Relation to Dopamine Receptor,” Oncology Reports 38, no. 1 (2017): 53-62.

[118]

D.-R. Pang, X.-Q. Su, Z.-X. Zhu, et al., “Flavonoid Dimers From the Total Phenolic Extract of Chinese Dragon's Blood, the Red Resin of Dracaena Cochinchinensis,” Fitoterapia 115 (2016): 135-141.

[119]

Q. Yuan, C. Qu, and C. Liu, “Summary of the Modern Clinical Application of Resina Draconis,” Medicinal Plant 4, no. 8 (2013): 64.

[120]

X. Chen, Y. Zhao, A. Yang, et al., “Chinese Dragon's Blood EtOAc Extract Inhibits Liver Cancer Growth Through Downregulation of Smad3,” Frontiers in Pharmacology 11 (2020): 530347.

[121]

L. Ma, H. Jiang, X. Xu, et al., “Tanshinone IIA Mediates SMAD7-YAP Interaction to Inhibit Liver Cancer Growth by Inactivating the Transforming Growth Factor Beta Signaling Pathway,” Aging (Albany NY) 11, no. 21 (2019): 9719.

[122]

L. Lu, Q. Guo, and L. Zhao, “Overview of Oroxylin A: A Promising Flavonoid Compound,” Phytotherapy Research 30, no. 11 (2016): 1765-1774.

[123]

H.-B. Li and F. Chen, “Isolation and Purification of Baicalein, Wogonin and Oroxylin A From the Medicinal Plant Scutellaria baicalensis by High-speed Counter-current Chromatography,” Journal of Chromatography A 1074, no. 1-2 (2005): 107-110.

[124]

Y. Sun, N. Lu, Y. Ling, et al., “Oroxylin A Suppresses Invasion Through Down-regulating the Expression of Matrix Metalloproteinase-2/9 in MDA-MB-435 human Breast Cancer Cells,” European Journal of Pharmacology 603, no. 1-3 (2009): 22-28.

[125]

L. Wei, Y. Yao, K. Zhao, et al., “Oroxylin A Inhibits Invasion and Migration Through Suppressing ERK/GSK-3β Signaling in Snail-expressing Non-small-cell Lung Cancer Cells,” Molecular Carcinogenesis 55, no. 12 (2016): 2121-2134.

[126]

T.-X. Huo, X.-P. Wang, Z. Yu, et al., “Oroxylin A Inhibits the Migration of Hepatocellular Carcinoma Cells by Inducing NAG-1 Expression,” Acta Pharmacologica Sinica 43, no. 3 (2022): 724-734.

[127]

M. Asif Ali, N. Khan, N. Kaleem, et al., “Anticancer Properties of sulforaphane: Current Insights at the Molecular Level,” Frontiers in Oncology 13 (2023): 1168321.

[128]

J. Wu, J. Han, B. Hou, C. Deng, H. Wu, and L. Shen, “Sulforaphane Inhibits TGF-β-induced Epithelial-mesenchymal Transition of Hepatocellular Carcinoma Cells via the Reactive Oxygen Species-dependent Pathway,” Oncology Reports 35, no. 5 (2016): 2977-2983.

[129]

N. Zhang, Y. Hu, C. Ding, et al., “Salvianolic Acid B Protects Against Chronic Alcoholic Liver Injury via SIRT1-mediated Inhibition of CRP and ChREBP in Rats,” Toxicology Letters 267 (2017): 1-10.

[130]

Y. Gong, D. Li, L. Li, et al., “Smad3 C-terminal Phosphorylation Site Mutation Attenuates the Hepatoprotective Effect of Salvianolic Acid B Against Hepatocarcinogenesis,” Food and Chemical Toxicology 147 (2021): 111912.

[131]

X.-N. Liu, S. Wang, Q. Yang, Y.-J. Wang, D.-X. Chen, and X.-X. Zhu, “ESC Reverses Epithelial Mesenchymal Transition Induced by Transforming Growth Factor-β via Inhibition of Smad Signal Pathway in HepG2 Liver Cancer Cells,” Cancer Cell International 15 (2015): 1-10.

[132]

Y.-J. Lee, E.-S. Kao, C.-Y. Chu, W.-L. Lin, Y.-H. Chiou, and T.-H. Tseng, “Inhibitory Effect of Ailanthoidol on 12-O-tetradecanoyl-phorbol-13-acetate-induced Tumor Promotion in Mouse Skin,” Oncology Reports 16, no. 4 (2006): 921-927.

[133]

J. K. Kim and J. G. Jun, “Ailanthoidol Suppresses Lipopolysaccharide-stimulated Inflammatory Reactions in RAW264. 7 Cells and Endotoxin Shock in Mice,” Journal of Cellular Biochemistry 112, no. 12 (2011): 3816-3823.

[134]

J.-H. Park, J.-G. Jun, and J.-K. Kim, “Anti-Adipogenic Activity of Ailanthoidol on 3T3-L1 Adipocytes,” Biomedical Science Letters 20, no. 2 (2014): 62-69.

[135]

T. Tseng, H. Lee, and Y. Lee, “Ailanthoidol, a Neolignan, Suppresses TGF-β1-induced HepG2 Hepatoblastoma Cell Progression,” Biomedicines 9 (2021): 1110.

[136]

C.-W. Lu, S.-K. Huang, T.-Y. Lin, and S.-J. Wang, “Echinacoside, an Active Constituent of Herba Cistanche, Suppresses Epileptiform Activity in Hippocampal CA3 Pyramidal Neurons,” The Korean Journal of Physiology & Pharmacology: Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology 22, no. 3 (2018): 249.

[137]

W. Li, J. Zhou, Y. Zhang, et al., “Echinacoside Exerts Anti-tumor Activity via the miR-503-3p/TGF-β1/Smad Aixs in Liver Cancer,” Cancer Cell International 21, no. 1 (2021): 304.

[138]

S. Liang, Y. Zou, J. Gao, et al., “The Chinese Medicine, Jiedu Recipe, Inhibits the Epithelial Mesenchymal Transition of Hepatocellular Carcinoma via the Regulation of smad2/3 Dependent and Independent Pathways,” Evidence-Based Complementary and Alternative Medicine 2018 (2018): 9780826.

[139]

J. Gao, Y. Ying, J. Wang, and Y. Cui, “Solanine Inhibits Immune Escape Mediated by Hepatoma Treg Cells via the Tgfβ/Smad Signaling Pathway,” BioMed Research International 2020 (2020): 9749631.

[140]

L. Zhang, Q. Y. Cai, J. Liu, et al., “Ursolic Acid Suppresses the Invasive Potential of Colorectal Cancer Cells by Regulating the TGF-beta1/ZEB1/miR-200c Signaling Pathway,” Oncology Letters 18, no. 3 (2019): 3274-3282.

[141]

L. L. Coutinho, T. C. T. Junior, and M. C. Rangel, “Sulforaphane: An Emergent Anti-cancer Stem Cell Agent,” Frontiers in Oncology 13 (2023): 1089115.

[142]

A. Mahn and A. Castillo, “Potential of Sulforaphane as a Natural Immune System Enhancer: A Review,” Molecules (Basel, Switzerland) 26, no. 3 (2021): 752.

[143]

B. M. Kaminski, S. M. Loitsch, M. J. Ochs, et al., “Isothiocyanate Sulforaphane Inhibits Protooncogenic Ornithine Decarboxylase Activity in Colorectal Cancer Cells via Induction of the TGF-beta/Smad Signaling Pathway,” Molecular Nutrition & Food Research 54, no. 10 (2010): 1486-1496.

[144]

Q. Hu, W. Zhang, Z. Wu, et al., “Baicalin and the Liver-gut System: Pharmacological Bases Explaining Its Therapeutic Effects,” Pharmacological Research 165 (2021): 105444.

[145]

X. Guan, S. Shen, J. Liu, et al., “Protective Effecs of Baicalin Magnesium on Non-alcoholic Steatohepatitis Rats Are Based on Inhibiting NLRP3/Caspase-1/IL-1beta Signaling Pathway,” BMC Complementary Medicine and Therapies 23, no. 1 (2023): 72.

[146]

B. Yang, H. Bai, Y. Sa, P. Zhu, and P. Liu, “Inhibiting EMT, Stemness and Cell Cycle Involved in Baicalin-induced Growth Inhibition and Apoptosis in Colorectal Cancer Cells,” Journal of Cancer 11, no. 8 (2020): 2303-2317.

[147]

Y. Xiong, J. Wang, H. Zhu, L. Liu, and Y. Jiang, “Chronic Oxymatrine Treatment Induces Resistance and Epithelial‑Mesenchymal Transition Through Targeting the Long Non-coding RNA MALAT1 in Colorectal Cancer Cells,” Oncology Reports 39, no. 3 (2018): 967-976.

[148]

X. Wang, C. Liu, J. Wang, Y. Fan, Z. Wang, and Y. Wang, “Oxymatrine Inhibits the Migration of human Colorectal Carcinoma RKO Cells via Inhibition of PAI-1 and the TGF-beta1/Smad Signaling Pathway,” Oncology Reports 37, no. 2 (2017): 747-753.

[149]

S. C. Tsai, W. C. Wu, and J. S. Yang, “Tetrandrine Inhibits Epithelial-Mesenchymal Transition in IL-6-Induced HCT116 Human Colorectal Cancer Cells,” OncoTargets and Therapy 14 (2021): 4523-4536.

[150]

S. Ben Hamouda and K. Essafi-Benkhadir, “Interplay Between Signaling Pathways and Tumor Microenvironment Components: A Paradoxical Role in Colorectal Cancer,” International Journal of Molecular Sciences 24, no. 6 (2023): 5600.

[151]

Q. Z. Chen, Y. Li, Y. Shao, et al., “TGF-beta1/PTEN/PI3K Signaling Plays a Critical Role in the Anti-proliferation Effect of Tetrandrine in human Colon Cancer Cells,” International Journal of Oncology 50, no. 3 (2017): 1011-1021.

[152]

B. Kou, W. Liu, W. Zhao, et al., “Thymoquinone Inhibits Epithelial-mesenchymal Transition in Prostate Cancer Cells by Negatively Regulating the TGF-beta/Smad2/3 Signaling Pathway,” Oncology Reports 38, no. 6 (2017): 3592-3598.

[153]

S. Katta, A. Srivastava, R. L. Thangapazham, et al., “Curcumin-Gene Expression Response in Hormone Dependent and Independent Metastatic Prostate Cancer Cells,” International Journal of Molecular Sciences 20, no. 19 (2019): 4891.

[154]

X. Liu, Y.-S. Piao, and J. T. Arnold, “Transforming Growth Factor β1 Increase of Hydroxysteroid Dehydrogenase Proteins Is Partly Suppressed by Red Clover Isoflavones in human Primary Prostate Cancer-derived Stromal Cells,” Carcinogenesis 32, no. 11 (2011): 1648-1654.

[155]

N. Dalpatraj, J. Tak, A. Naik, and N. Thakur, “Hesperetin Modulates TGFβ Induced Metastatic Potential of Prostate Cancer Cells by Altering Histone Methylation Marks,” Advances in Cancer Biology—Metastasis 6 (2022): 100077.

[156]

M. M. Baruah, A. P. Khandwekar, and N. Sharma, “Quercetin Modulates Wnt Signaling Components in Prostate Cancer Cell Line by Inhibiting Cell Viability, Migration, and Metastases,” Tumour Biology: The Journal of the International Society for Oncodevelopmental Biology and Medicine 37, no. 10 (2016): 14025-14034.

[157]

B. S. Pollard, M. A. Suckow, W. R. Wolter, et al., “Digitoxin Inhibits Epithelial-to-Mesenchymal-Transition in Hereditary Castration Resistant Prostate Cancer,” Frontiers in Oncology 9 (2019): 630.

[158]

Y. C. Wen, W. J. Lee, P. Tan, et al., “By Inhibiting Snail Signaling and miR-23a-3p, osthole Suppresses the EMT-mediated Metastatic Ability in Prostate Cancer,” Oncotarget 6, no. 25 (2015): 21120-21136.

[159]

S. Terzioglu-Usak, M. T. Yildiz, B. Goncu, and N. Ozten-Kandas, “Achieving the Balance: Biphasic Effects of Genistein on PC-3 Cells,” Journal of Food Biochemistry 43, no. 8 (2019): e12951.

[160]

S. Mirzoeva, C. A. Franzen, and J. C. Pelling, “Apigenin Inhibits TGF-beta-induced VEGF Expression in human Prostate Carcinoma Cells via a Smad2/3- and Src-dependent Mechanism,” Molecular Carcinogenesis 53, no. 8 (2014): 598-609.

[161]

H. J. Ting, G. Deep, A. K. Jain, et al., “Silibinin Prevents Prostate Cancer Cell-mediated Differentiation of Naïve Fibroblasts Into Cancer-associated Fibroblast Phenotype by Targeting TGF β2,” Molecular Carcinogenesis 54, no. 9 (2015): 730-741.

[162]

S. Shan, M. Su, H. Wang, et al., “Y-27632 Targeting ROCK1&2 Modulates Cell Growth, Fibrosis and Epithelial-mesenchymal Transition in Hyperplastic Prostate by Inhibiting β-catenin Pathway,” Molecular Biomedicine 5, no. 1 (2024): 52.

[163]

S. E. Campbell, B. Rudder, R. B. Phillips, et al., “γ-Tocotrienol Induces Growth Arrest Through a Novel Pathway With TGFβ2 in Prostate Cancer,” Free Radical Biology and Medicine 50, no. 10 (2011): 1344-1354.

[164]

X. P. Shi, S. Miao, Y. Wu, et al., “Resveratrol Sensitizes Tamoxifen in Antiestrogen-resistant Breast Cancer Cells With Epithelial-mesenchymal Transition Features,” International Journal of Molecular Sciences 14, no. 8 (2013): 15655-15668.

[165]

Z. Yang, A. Garcia, S. Xu, et al., “Withania Somnifera Root Extract Inhibits Mammary Cancer Metastasis and Epithelial to Mesenchymal Transition,” PLoS ONE 8, no. 9 (2013): e75069.

[166]

M. M. Al-Ansari and A. Aboussekhra, “Caffeine Mediates Sustained Inactivation of Breast Cancer-associated Myofibroblasts via Up-regulation of Tumor Suppressor Genes,” PLoS ONE 9, no. 3 (2014): e90907.

[167]

J. Lee, E. R. Hahm, A. I. Marcus, and S. V. Singh, “Withaferin A Inhibits Experimental Epithelial-mesenchymal Transition in MCF-10A Cells and Suppresses Vimentin Protein Level in Vivo in Breast Tumors,” Molecular Carcinogenesis 54, no. 6 (2015): 417-429.

[168]

G. M. Adinew, E. Taka, B. Mochona, et al., “Therapeutic Potential of Thymoquinone in Triple-Negative Breast Cancer Prevention and Progression Through the Modulation of the Tumor Microenvironment,” Nutrients 14, no. 1 (2021): 79.

[169]

N. M. Elsherbiny and M. M. Al-Gayyar, “Anti-tumor Activity of Arjunolic Acid Against Ehrlich Ascites Carcinoma Cells in Vivo and in Vitro Through Blocking TGF-beta Type 1 Receptor,” Biomedicine & Pharmacotherapy 82 (2016): 28-34.

[170]

P. Paramita, B. W. Wardhani, S. I. Wanandi, and M. Louisa, “Curcumin for the Prevention of Epithelial-Mesenchymal Transition in Endoxifen-Treated MCF-7 Breast Cancer Cel,” Asian Pacific Journal of Cancer Prevention 19, no. 5 (2018): 1243-1249.

[171]

J. Lee, “3,3'-Diindolylmethane Inhibits TNF-alpha- and TGF-beta-Induced Epithelial-Mesenchymal Transition in Breast Cancer Cells,” Nutrition and Cancer 71, no. 6 (2019): 992-1006.

[172]

C. Allegretta, G. Difonzo, F. Caponio, G. Tamma, and O. Laselva, “Olive Leaf Extract (OLE) as a Novel Antioxidant That Ameliorates the Inflammatory Response in Cystic Fibrosis,” Cells 12, no. 13 (2023): 1764.

[173]

P. Nath, D. Majumder, R. Debnath, M. Debnath, S. Singh Sekhawat, and D. Maiti, “Immunotherapeutic Potential of Ethanolic Olive Leaves Extract (EOLE) and IL-28B Combination Therapy in ENU Induced Animal Model of Leukemia,” Cytokine 156 (2022): 155913.

[174]

Z. Habli, G. Toumieh, M. Fatfat, O. N. Rahal, and H. Gali-Muhtasib, “Emerging Cytotoxic Alkaloids in the Battle Against Cancer: Overview of Molecular Mechanisms,” Molecules (Basel, Switzerland) 22, no. 2 (2017): 250.

[175]

E. Azzini, S. I. Peña-Corona, H. Hernández-Parra, et al., “Neuroprotective and Anti-inflammatory Effects of Curcumin in Alzheimer's Disease: Targeting Neuroinflammation Strategies,” Phytotherapy Research 38, no. 6 (2024): 3169-3189.

[176]

E. Azzini, L. Barnaba, M. Mattera, D. Calina, J. Sharifi-Rad, and W. C. Cho, “Updated Evidence on Raspberries as Functional Foods: Anticancer Bioactivity and Therapeutic Implications,” Food Frontiers 5, no. 6 (2024): 2351-2382.

[177]

P. Chaudhary, P. Janmeda, A. O. Docea, et al., “Oxidative Stress, Free Radicals and Antioxidants: Potential Crosstalk in the Pathophysiology of human Diseases,” Frontiers in Chemistry 11 (2023): 1158198.

[178]

P. Chaudhary, D. Mitra, P. K. Das Mohapatra, et al., “Camellia Sinensis: Insights on Its Molecular Mechanisms of Action towards Nutraceutical, Anticancer Potential and Other Therapeutic Applications,” Arabian Journal of Chemistry 16, no. 5 (2023): 104680.

[179]

A. K. Calgarotto, A. L. Longhini, F. V. Pericole de Souza, et al., “Immunomodulatory Effect of Green Tea Treatment in Combination With Low-dose Chemotherapy in Elderly Acute Myeloid Leukemia Patients With Myelodysplasia-related Changes,” Integrative Cancer Therapies 20 (2021): 15347354211002647.

[180]

G. D'Arena, V. Simeon, L. De Martino, et al., “Regulatory T-Cell Modulation by Green Tea in Chronic Lymphocytic Leukemia,” International Journal of Immunopathology and Pharmacology 26, no. 1 (2013): 117-125.

[181]

clinicaltrials.gov. Phase II Study of Curcumin vs Placebo for Chemotherapy-Treated Breast Cancer Patients Undergoing Radiotherapy. Accessed 25 November 2023, https://clinicaltrials.gov/study/NCT01740323

[182]

NCT03232138 Cg. Clinical Trial of Lung Cancer Chemoprevention With Sulforaphane in Former Smokers. Accessed 15 July 2024, https://clinicaltrials.gov/study/NCT03232138

[183]

H. Wang, Y. Chen, L. Wang, Q. Liu, S. Yang, and C. Wang, “Advancing Herbal Medicine: Enhancing Product Quality and Safety Through Robust Quality Control Practices,” Frontiers in pharmacology 14 (2023): 1265178.

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