AXL promotes malignant phenotypes in tumor cells and might be a potential antitumor target of natural products

Yuan Yuan, Shan Wang, Jia-Lei Fu, Xin-Xin Deng, Yang Guo, Zheng-Wang Guo, Shu-Yan Han

Adv. Chi. Med ›› 2024, Vol. 1 ›› Issue (4) : 179-189.

PDF(885 KB)
Adv. Chi. Med All Journals
PDF(885 KB)
Adv. Chi. Med ›› 2024, Vol. 1 ›› Issue (4) : 179-189. DOI: 10.1002/acm4.29
REVIEW ARTICLE

AXL promotes malignant phenotypes in tumor cells and might be a potential antitumor target of natural products

Author information +
History +

Abstract

AXL belongs to the TAM receptor tyrosine kinase family. Relying on binding its high‐affinity ligand—growth arrest‐specific protein 6 (Gas6)—AXL plays an important role in tumor initiation and progression. Traditional Chinese Medicine (TCM) has been clinically used in tumor treatment for a long time, and remarkable therapeutic efficacy has been achieved. Recent studies pointed out that some natural products derived from TCM could inhibit tumor growth by targeting AXL. The potential antitumor mechanisms of natural products targeting AXL still need to be understood. In this review, we discussed the relationship between the AXL axis and tumor malignant phenotype, including migration, invasion, drug resistance, and immunosuppression. The effects and mechanisms of natural products on targeting AXL in tumors also have been systematically summarized.

Keywords

AXL / cancer treatment / natural product / receptor tyrosine kinase / signaling pathway

Cite this article

Download citation ▾
Yuan Yuan, Shan Wang, Jia-Lei Fu, Xin-Xin Deng, Yang Guo, Zheng-Wang Guo, Shu-Yan Han. AXL promotes malignant phenotypes in tumor cells and might be a potential antitumor target of natural products. Adv. Chi. Med, 2024, 1(4): 179‒189 https://doi.org/10.1002/acm4.29

References

[1]
Hanahan D . Hallmarks of cancer: new dimensions. Cancer Discov. 2022; 12 (1): 31- 46.
CrossRef Google scholar
[2]
Huang L , Jiang S , Shi Y . Tyrosine kinase inhibitors for solid tumors in the past 20 years (2001-2020). J Hematol Oncol. 2020; 13 (1): 143.
CrossRef Google scholar
[3]
Butti R , Das S , Gunasekaran VP , Yadav AS , Kumar D , Kundu GC . Receptor tyrosine kinases (RTKs) in breast cancer: signaling, therapeutic implications and challenges. Mol Cancer. 2018; 17 (1): 34.
CrossRef Google scholar
[4]
Huang L , Fu L . Mechanisms of resistance to EGFR tyrosine kinase inhibitors. Acta Pharm Sin B. 2015; 5 (5): 390- 401.
CrossRef Google scholar
[5]
Niederst MJ , Engelman JA . Bypass mechanisms of resistance to receptor tyrosine kinase inhibition in lung cancer. Sci Signal. 2013; 6 (294): re6.
CrossRef Google scholar
[6]
Luo M , Fu LW . Redundant kinase activation and resistance of EGFR-tyrosine kinase inhibitors. Am J Cancer Res. 2014; 4 (6): 608- 628.
[7]
Scaltriti M , Elkabets M , Baselga J . Molecular pathways: AXL, a membrane receptor mediator of resistance to therapy. Clin Cancer Res. 2016; 22 (6): 1313- 1317.
CrossRef Google scholar
[8]
Landers SM , Bhalla AD , Ma X , et al. AXL inhibition enhances MEK inhibitor sensitivity in malignant peripheral nerve sheath tumors. J Cancer Sci Clin Ther. 2020; 4 (4): 511- 525.
CrossRef Google scholar
[9]
Liu L , Greger J , Shi H , et al. Novel mechanism of lapatinib resistance in HER2-positive breast tumor cells: activation of AXL. Cancer Res. 2009; 69 (17): 6871- 6878.
CrossRef Google scholar
[10]
Han S , Wang Y , Ge C , et al. Pharmaceutical inhibition of AXL suppresses tumor growth and invasion of esophageal squamous cell carcinoma. Exp Ther Med. 2020; 20 (5): 41.
CrossRef Google scholar
[11]
Jiang C , Cheng Z , Jiang T , Xu Y , Wang B . MicroRNA-34a inhibits cell invasion and epithelial-mesenchymal transition via targeting AXL/PI3K/AKT/Snail signaling in nasopharyngeal carcinoma. Genes Genomics. 2020; 42 (8): 971- 978.
CrossRef Google scholar
[12]
Tanaka M , Siemann DW . Gas6/Axl signaling pathway in the tumor immune microenvironment. Cancers. 2020; 12 (7): 1850.
CrossRef Google scholar
[13]
Bumm CV , Folwaczny M , Wolfle UC . Necrotizing periodontitis or medication-related osteonecrosis of the jaw (MRONJ) in a patient receiving Bemcentinib-a case report. Oral Maxillofac Surg. 2020; 24 (3): 353- 358.
CrossRef Google scholar
[14]
Atanasov AG , Waltenberger B , Pferschy-Wenzig EM , et al. Discovery and resupply of pharmacologically active plant-derived natural products: a review. Biotechnol Adv. 2015; 33 (8): 1582- 1614.
CrossRef Google scholar
[15]
Efferth T . From ancient herb to modern drug: Artemisia annua and artemisinin for cancer therapy. Semin Cancer Biol. 2017; 46: 65- 83.
CrossRef Google scholar
[16]
Kim NY , Yang IJ , Kim S , Lee C . Lotus (Nelumbo nucifera) seedpod extract inhibits cell proliferation and induces apoptosis in non-small cell lung cancer cells via down-regulation of Axl. J Food Biochem. 2021; 45 (2): e13601.
CrossRef Google scholar
[17]
Jeong I , Song J , Bae SY , Lee SK . Overcoming the intrinsic gefitinib-resistance via downregulation of AXL in non-small cell lung cancer. J Cancer Prev. 2019; 24 (4): 217- 223.
CrossRef Google scholar
[18]
Graham DK , DeRyckere D , Davies KD , Earp HS . The TAM family: phosphatidylserine sensing receptor tyrosine kinases gone awry in cancer. Nat Rev Cancer. 2014; 14 (12): 769- 785.
CrossRef Google scholar
[19]
Linger RMA , Keating AK , Earp HS , Graham DK . TAM receptor tyrosine kinases: biologic functions, signaling, and potential therapeutic targeting in human cancer. Adv Cancer Res. 2008; 100 (100): 35- 83.
CrossRef Google scholar
[20]
Colavito, SA . AXL as a target in breast cancer therapy. J Oncol. 2020; 5291952.
CrossRef Google scholar
[21]
Zhu CJ , Wei YQ , Wei XW . AXL receptor tyrosine kinase as a promising anti-cancer approach: functions, molecular mechanisms and clinical applications. Mol Cancer. 2019; 18 (1): 153.
CrossRef Google scholar
[22]
Fridell YWC , Jin Y , Quilliam LA , et al. Differential activation of the Ras/extracellular-signal-regulated protein kinase pathway is responsible for the biological consequences induced by the Axl receptor tyrosine kinase. Mol Cell Biol. 1996; 16 (1): 135- 145.
CrossRef Google scholar
[23]
Paccez JD , Vasques GJ , Correa RG , et al. The receptor tyrosine kinase Axl is an essential regulator of prostate cancer proliferation and tumor growth and represents a new therapeutic target. Oncogene. 2013; 32 (6): 689- 698.
CrossRef Google scholar
[24]
Tai KY , Shieh YS , Lee CS , Shiah SG , Wu CW . Axl promotes cell invasion by inducing MMP-9 activity through activation of NF-kappaB and Brg-1. Oncogene. 2008; 27 (29): 4044- 4055.
CrossRef Google scholar
[25]
Burstyn-Cohen T , Maimon A . TAM receptors, phosphatidylserine, inflammation, and cancer. Cell Commun Signal. 2019; 17 (1): 156.
CrossRef Google scholar
[26]
Caberoy NB , Alvarado G , Bigcas JL , Li W . Galectin-3 is a new MerTK-specific eat-me signal. J Cell Physiol. 2012; 227 (2): 401- 407.
CrossRef Google scholar
[27]
Caberoy NB , Zhou Y , Li W . Tubby and tubby-like protein 1 are new MerTK ligands for phagocytosis. EMBO J. 2010; 29 (23): 3898- 3910.
CrossRef Google scholar
[28]
Konishi A , Aizawa T , Mohan A , Korshunov VA , Berk BC . Hydrogen peroxide activates the Gas6-Axl pathway in vascular smooth muscle cells. J Biol Chem. 2004; 279 (27): 28766- 28770.
CrossRef Google scholar
[29]
Talmadge JE , Fidler IJ . AACR centennial series: the biology of cancer metastasis: historical perspective. Cancer Res. 2010; 70 (14): 5649- 5669.
CrossRef Google scholar
[30]
Abu-Thuraia A , Gauthier R , Chidiac R , et al. Axl phosphorylates Elmo Scaffold proteins to promote rac activation and cell invasion. Mol Cell Biol. 2015; 35 (1): 76- 87.
CrossRef Google scholar
[31]
Xu JC , Jia L , Ma HY , Li YP , Ma ZH , Zhao YF . Axl gene knockdown inhibits the metastasis properties of hepatocellular carcinoma via PI3K/Akt-PAK1 signal pathway. Tumor Biol. 2014; 35 (4): 3809- 3817.
CrossRef Google scholar
[32]
Revach OY , Sandler O , Samuels Y , Geiger B . Cross-talk between receptor tyrosine kinases AXL and ERBB3 regulates invadopodia formation in melanoma cells. Cancer Res. 2019; 79 (10): 2634- 2648.
CrossRef Google scholar
[33]
Zdzalik-Bielecka D , Poswiata A , Kozik K , et al. The GAS6-AXL signaling pathway triggers actin remodeling that drives membrane ruffling, macropinocytosis, and cancer-cell invasion. Proc Natl Acad Sci USA. 2021; 118 (28): e2024596118.
CrossRef Google scholar
[34]
Kessenbrock K , Plaks V , Werb Z . Matrix metalloproteinases: regulators of the tumor microenvironment. Cell. 2010; 141 (1): 52- 67.
CrossRef Google scholar
[35]
Reichl P , Dengler M , van Zijl F , et al. Axl activates autocrine transforming growth factor-beta signaling in hepatocellular carcinoma. Hepatology. 2015; 61 (3): 930- 941.
CrossRef Google scholar
[36]
Li YY , Tao YW , Gao S , et al. Cancer-associated fibroblasts contribute to oral cancer cells proliferation and metastasis via exosome-mediated paracrine miR-34a-5p. EBioMedicine. 2018; 36: 209- 220.
CrossRef Google scholar
[37]
Antony J , Huang RYJ . AXL-driven EMT state as a targetable conduit in cancer. Cancer Res. 2017; 77 (14): 3725- 3732.
CrossRef Google scholar
[38]
Polyak K , Weinberg RA . Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer. 2009; 9 (4): 265- 273.
CrossRef Google scholar
[39]
Puram SV , Tirosh I , Parikh AS , et al. Single-cell transcriptomic analysis of primary and metastatic tumor ecosystems in head and neck cancer. Cell. 2017; 171 (7): 1611- 1624.e24.
CrossRef Google scholar
[40]
Koorstra JB , Karikari CA , Feldmann G , et al. The Axl receptor tyrosine kinase confers an adverse prognostic influence in pancreatic cancer and represents a new therapeutic target. Cancer Biol Ther. 2009; 8 (7): 618- 626.
CrossRef Google scholar
[41]
Leconet W , Chentouf M , du Manoir S , et al. Therapeutic activity of anti-AXL antibody against triple-negative breast cancer patient-derived xenografts and metastasis. Clin Cancer Res. 2017; 23 (11): 2806- 2816.
CrossRef Google scholar
[42]
Asiedu MK , Beauchamp-Perez FD , Ingle JN , Behrens MD , Radisky DC , Knutson KL . AXL induces epithelial-to-mesenchymal transition and regulates the function of breast cancer stem cells. Oncogene. 2014; 33 (10): 1316- 1324.
CrossRef Google scholar
[43]
Vuoriluoto K , Haugen H , Kiviluoto S , et al. Vimentin regulates EMT induction by Slug and oncogenic H-Ras and migration by governing Axl expression in breast cancer. Oncogene. 2011; 30 (12): 1436- 1448.
CrossRef Google scholar
[44]
Hua WF , Zhao Y , Jin XH , et al. METTL3 promotes ovarian carcinoma growth and invasion through the regulation of AXL translation and epithelial to mesenchymal transition. Gynecol Oncol. 2018; 151 (2): 356- 365.
CrossRef Google scholar
[45]
Vasan N , Baselga J , Hyman DM . A view on drug resistance in cancer. Nature. 2019; 575 (7782): 299- 309.
CrossRef Google scholar
[46]
Dufies M , Jacquel A , Belhacene N , et al. Mechanisms of AXL overexpression and function in Imatinib-resistant chronic myeloid leukemia cells. Oncotarget. 2011; 2 (11): 874- 885.
CrossRef Google scholar
[47]
Ben-Batalla I , Erdmann R , Jorgensen H , et al. Axl blockade by BGB324 inhibits BCR-ABL tyrosine kinase inhibitor-sensitive and -resistant chronic myeloid leukemia. Clin Cancer Res. 2017; 23 (9): 2289- 2300.
CrossRef Google scholar
[48]
Gioia R , Tregoat C , Dumas PY , et al. CBL controls a tyrosine kinase network involving AXL, SYK and LYN in nilotinib-resistant chronic myeloid leukaemia. J Pathol. 2015; 237 (1): 14- 24.
CrossRef Google scholar
[49]
Meyer AS , Miller MA , Gertler FB , Lauffenburger DA . The receptor AXL diversifies EGFR signaling and limits the response to EGFR-targeted inhibitors in triple-negative breast cancer cells. Sci Signal. 2013; 6 (287): ra66.
CrossRef Google scholar
[50]
Vouri M , Croucher DR , Kennedy SP , An Q , Pilkington GJ , Hafizi S . Axl-EGFR receptor tyrosine kinase hetero-interaction provides EGFR with access to pro-invasive signalling in cancer cells. Oncogenesis. 2016; 5 (10): e266.
CrossRef Google scholar
[51]
McDaniel NK , Iida M , Nickel KP , et al. AXL mediates cetuximab and radiation resistance through tyrosine 821 and the c-ABL kinase pathway in head and neck cancer. Clin Cancer Res. 2020; 26 (16): 4349- 4359.
CrossRef Google scholar
[52]
Bansal N , Mishra PJ , Stein M , DiPaola RS , Bertino JR . Axl receptor tyrosine kinase is up-regulated in metformin resistant prostate cancer cells. Oncotarget. 2015; 6 (17): 15321- 15331.
CrossRef Google scholar
[53]
Lin JZ , Wang ZJ , De W , et al. Targeting AXL overcomes resistance to docetaxel therapy in advanced prostate cancer. Oncotarget. 2017; 8 (25): 41064- 41077.
CrossRef Google scholar
[54]
Ghosh S . Cisplatin: the first metal based anticancer drug. Bioorg Chem. 2019; 88: 102925.
CrossRef Google scholar
[55]
Baize N , Monnet I , Greillier L , et al. Carboplatin plus etoposide versus topotecan as second-line treatment for patients with sensitive relapsed small-cell lung cancer: an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2020; 21 (9): 1224- 1233.
CrossRef Google scholar
[56]
Carvalho C , Santos RX , Cardoso S , et al. Doxorubicin: the good, the bad and the ugly effect. Curr Med Chem. 2009; 16 (25): 3267- 3285.
CrossRef Google scholar
[57]
Hainsworth JD , Greco FA . Etoposide: twenty years later. Ann Oncol. 1995; 6 (4): 325- 341.
CrossRef Google scholar
[58]
Linger RM , Cohen RA , Cummings CT , et al. Mer or Axl receptor tyrosine kinase inhibition promotes apoptosis, blocks growth and enhances chemosensitivity of human non-small cell lung cancer. Oncogene. 2013; 32 (29): 3420- 3431.
CrossRef Google scholar
[59]
Debruyne DN , Bhatnagar N , Sharma B , et al. ALK inhibitor resistance in ALK(F1174L)-driven neuroblastoma is associated with AXL activation and induction of EMT. Oncogene. 2016; 35 (28): 3681- 3691.
CrossRef Google scholar
[60]
Zhou L , Liu XD , Sun M , et al. Targeting MET and AXL overcomes resistance to sunitinib therapy in renal cell carcinoma. Oncogene. 2016; 35 (21): 2687- 2697.
CrossRef Google scholar
[61]
Creedon H , Gomez-Cuadrado L , Tarnauskaite Z , et al. Identification of novel pathways linking epithelial-to-mesenchymal transition with resistance to HER2-targeted therapy. Oncotarget. 2016; 7 (10): 11539- 11552.
CrossRef Google scholar
[62]
Wu Y , Ginther C , Kim J , et al. Expression of Wnt3 activates Wnt/beta-catenin pathway and promotes EMT-like phenotype in trastuzumab-resistant HER2-overexpressing breast cancer cells. Mol Cancer Res. 2012; 10 (12): 1597- 1606.
CrossRef Google scholar
[63]
Della Corte CM , Bellevicine C , Vicidomini G , et al. SMO gene amplification and activation of the hedgehog pathway as novel mechanisms of resistance to anti-epidermal growth factor receptor drugs in human lung cancer. Clin Cancer Res. 2015; 21 (20): 4686- 4697.
CrossRef Google scholar
[64]
Konen JM , Rodriguez BL , Padhye A , et al. Dual inhibition of MEK and AXL targets tumor cell heterogeneity and prevents resistant outgrowth mediated by the epithelial-to-mesenchymal transition in NSCLC. Cancer Res. 2021; 81 (5): 1398- 1412.
CrossRef Google scholar
[65]
Pitt JM , Marabelle A , Eggermont A , Soria JC , Kroemer G , Zitvogel L . Targeting the tumor microenvironment: removing obstruction to anticancer immune responses and immunotherapy. Ann Oncol. 2016; 27 (8): 1482- 1492.
CrossRef Google scholar
[66]
Son HY , Jeong HK . Immune evasion mechanism and AXL. Front Oncol. 2021; 11: 756225.
CrossRef Google scholar
[67]
Rothlin CV , Ghosh S , Zuniga EI , Oldstone MBA , Lemke G . TAM receptors are pleiotropic inhibitors of the innate immune response. Cell. 2007; 131 (6): 1124- 1136.
CrossRef Google scholar
[68]
Tsukita Y , Fujino N , Miyauchi E , et al. Axl kinase drives immune checkpoint and chemokine signalling pathways in lung adenocarcinomas. Mol Cancer. 2019; 18 (1): 24.
CrossRef Google scholar
[69]
Kasikara C , Kumar S , Kimani S , et al. Phosphatidylserine sensing by TAM receptors regulates AKT-dependent chemoresistance and PD-L1 expression. Mol Cancer Res. 2017; 15 (6): 753- 764.
CrossRef Google scholar
[70]
Guo ZQ , Li Y , Zhang DD , Ma JY . Axl inhibition induces the antitumor immune response which can be further potentiated by PD-1 blockade in the mouse cancer models. Oncotarget. 2017; 8 (52): 89761- 89774.
CrossRef Google scholar
[71]
Terry S , Abdou A , Engelsen AST , et al. AXL targeting overcomes human lung cancer cell resistance to NK- and CTL-mediated cytotoxicity. Cancer Immunol Res. 2019; 7 (11): 1789- 1802.
CrossRef Google scholar
[72]
Liu YT , Lai YH , Lin HH , Chen JH . Lotus seedpod extracts reduced lipid accumulation and lipotoxicity in hepatocytes. Nutrients. 2019; 11 (12): 2895.
CrossRef Google scholar
[73]
Shen Y , Guan Y , Song X , et al. Polyphenols extract from lotus seedpod (Nelumbo nucifera Gaertn.): phenolic compositions, antioxidant, and antiproliferative activities. Food Sci Nutr. 2019; 7 (9): 3062- 3070.
CrossRef Google scholar
[74]
Menke K , Schwermer M , Eisenbraun J , Schramm A , Zuzak TJ . Anticancer effects of Viscum album fraxini extract on medulloblastoma cells in vitro. Complement Med Res. 2021; 28 (1): 15- 22.
CrossRef Google scholar
[75]
Ucar EO , Arda N , Aitken A . Extract from mistletoe, Viscum album L. reduces Hsp27 and 14-3-3 protein expression and induces apoptosis in C6 rat glioma cells. Genet Mol Res. 2012; 11 (3): 2801- 2813.
CrossRef Google scholar
[76]
Kwon YS , Chun SY , Kim MK , Nan HY , Lee C , Kim S . Mistletoe extract targets the STAT3-FOXM1 pathway to induce apoptosis and inhibits metastasis in breast cancer cells. Am J Chin Med. 2021; 49 (2): 487- 504.
CrossRef Google scholar
[77]
Kim S , Kim KC , Lee C . Mistletoe (Viscum album) extract targets Axl to suppress cell proliferation and overcome cisplatin- and erlotinib-resistance in non-small cell lung cancer cells. Phytomedicine. 2017; 36: 183- 193.
CrossRef Google scholar
[78]
Han SY , Zhao W , Han HB , et al. Marsdenia tenacissima extract overcomes Axl- and Met-mediated erlotinib and gefitinib cross-resistance in non-small cell lung cancer cells. Oncotarget. 2017; 8 (34): 56893- 56905.
CrossRef Google scholar
[79]
Lai DW , Yu SJ , van Ofwegen L , Totzke F , Proksch P , Lin WH . 9,10-Secosteroids, protein kinase inhibitors from the Chinese Gorgonian Astrogorgia sp. Bioorg Med Chem. 2011; 19 (22): 6873- 6880.
CrossRef Google scholar
[80]
Nie YW , Li Y , Luo L , et al. Phytochemistry and pharmacological activities of the diterpenoids from the genus Daphne. Molecules. 2021; 26 (21): 6598.
CrossRef Google scholar
[81]
Hong JY , Nam JW , Seo EK , Lee SK . Daphnane diterpene esters with anti-proliferative activities against human lung cancer cells from Daphne genkwa. Chem Pharm Bull (Tokyo). 2010; 58 (2): 234- 237.
CrossRef Google scholar
[82]
Bang KK , Yun CY , Lee C , et al. Melanogenesis inhibitory daphnane diterpenoids from the flower buds of Daphne genkwa. Bioorg Med Chem Lett. 2013; 23 (11): 3334- 3337.
CrossRef Google scholar
[83]
Li S , Chou G , Hseu Y , Yang H , Kwan H , Yu Z . Isolation of anticancer constituents from flos genkwa (Daphne genkwa Sieb.et Zucc.) through bioassay-guided procedures. Chem Cent J. 2013; 7 (1): 159.
CrossRef Google scholar
[84]
Chen Y , Zhao CL , Dong W , et al. Tigliane-and daphnane-type diterpenoids from the buds of Daphne genkwa with their cytotoxic activities. Nat Prod Res. 2022; 37 (18): 1- 7.
CrossRef Google scholar
[85]
Bae SY , Hong JY , Lee HJ , Park HJ , Lee SK . Targeting the degradation of AXL receptor tyrosine kinase to overcome resistance in gefitinib-resistant non-small cell lung cancer. Oncotarget. 2015; 6 (12): 10146- 10160.
CrossRef Google scholar
[86]
Dai X , Zhang X , Chen W , et al. Dihydroartemisinin: a potential natural anticancer drug. Int J Biol Sci. 2021; 17 (2): 603- 622.
CrossRef Google scholar
[87]
Keating GM . Dihydroartemisinin/Piperaquine: a review of its use in the treatment of uncomplicated Plasmodium falciparum malaria. Drugs. 2012; 72 (7): 937- 961.
CrossRef Google scholar
[88]
Luo J , Zhang Y , Wang Y , et al. Artesunate and dihydroartemisinin inhibit rabies virus replication. Virol Sin. 2021; 36 (4): 721- 729.
CrossRef Google scholar
[89]
Chen B , Li C , Chang G , Wang H . Dihydroartemisinin targets fibroblast growth factor receptor 1 (FGFR1) to inhibit interleukin 17A (IL-17A)-induced hyperproliferation and inflammation of keratinocytes. Bioengineered. 2022; 13 (1): 1530- 1540.
CrossRef Google scholar
[90]
Yang DX , Qiu J , Zhou HH , et al. Dihydroartemisinin alleviates oxidative stress in bleomycin-induced pulmonary fibrosis. Life Sci. 2018; 205: 176- 183.
CrossRef Google scholar
[91]
Li X , Ba Q , Liu Y , et al. Dihydroartemisinin selectively inhibits PDGFRα-positive ovarian cancer growth and metastasis through inducing degradation of PDGFRα protein. Cell Discov. 2017; 3 (1): 17042.
CrossRef Google scholar
[92]
Cai X , Miao J , Sun R , et al. Dihydroartemisinin overcomes the resistance to osimertinib in EGFR-mutant non-small-cell lung cancer. Pharmacol Res. 2021; 170: 105701.
CrossRef Google scholar
[93]
Zhang F , Ma Q , Xu Z , et al. Dihydroartemisinin inhibits TCTP-dependent metastasis in gallbladder cancer. J Exp Clin Cancer Res. 2017; 36 (1): 68.
CrossRef Google scholar
[94]
Lu JJ , Chen SM , Zhang XW , Ding J , Meng LH . The anti-cancer activity of dihydroartemisinin is associated with induction of iron-dependent endoplasmic reticulum stress in colorectal carcinoma HCT116 cells. Invest New Drugs. 2011; 29 (6): 1276- 1283.
CrossRef Google scholar
[95]
Zhou ZH , Chen FX , Xu WR , et al. Enhancement effect of dihydroartemisinin on human gammadelta T cell proliferation and killing pancreatic cancer cells. Int Immunopharmacol. 2013; 17 (3): 850- 857.
CrossRef Google scholar
[96]
Han W , Duan X , Ni K , Li Y , Chan C , Lin W . Co-delivery of dihydroartemisinin and pyropheophorbide-iron elicits ferroptosis to potentiate cancer immunotherapy. Biomaterials. 2022; 280: 121315.
CrossRef Google scholar
[97]
Paccez JD , Duncan K , Sekar D , et al. Dihydroartemisinin inhibits prostate cancer via JARID2/miR-7/miR-34a-dependent downregulation of Axl. Oncogenesis. 2019; 8 (3): 14.
CrossRef Google scholar
[98]
Hansen TB , Kjems J , Damgaard CK . Circular RNA and miR-7 in cancer. Cancer Res. 2013; 73 (18): 5609- 5612.
CrossRef Google scholar
[99]
Li S , Wei X , He J , et al. The comprehensive landscape of miR-34a in cancer research. Cancer Metastasis Rev. 2021; 40 (3): 925- 948.
CrossRef Google scholar
[100]
Zielińska A , Alves H , Marques V , et al. Properties, extraction methods, and delivery systems for curcumin as a natural source of beneficial health effects. Medicina. 2020; 56 (7): 336.
CrossRef Google scholar
[101]
Fu YS , Chen TH , Weng L , Huang L , Lai D , Weng CF . Pharmacological properties and underlying mechanisms of curcumin and prospects in medicinal potential. Biomed Pharmacother. 2021; 141: 111888.
CrossRef Google scholar
[102]
Anand P , Sundaram C , Jhurani S , Kunnumakkara AB , Aggarwal BB . Curcumin and cancer: an "old-age" disease with an "age-old" solution. Cancer Lett. 2008; 267 (1): 133- 164.
CrossRef Google scholar
[103]
Wang M , Jiang S , Zhou L , et al. Potential mechanisms of action of curcumin for cancer prevention: focus on cellular signaling pathways and miRNAs. Int J Biol Sci. 2019; 15 (6): 1200- 1214.
CrossRef Google scholar
[104]
Gallardo M , Kemmerling U , Aguayo F , Bleak TC , Munoz JP , Calaf GM . Curcumin rescues breast cells from epithelial-mesenchymal transition and invasion induced by anti-miR-34a. Int J Oncol. 2020; 56 (2): 480- 493.
CrossRef Google scholar
[105]
Ma J , Fang B , Zeng F , et al. Curcumin inhibits cell growth and invasion through up-regulation of miR-7 in pancreatic cancer cells. Toxicol Lett. 2014; 231 (1): 82- 91.
CrossRef Google scholar
[106]
Fu J , Wang Z , Huang L , et al. Review of the botanical characteristics, phytochemistry, and pharmacology of Astragalus membranaceus (Huangqi). Phytother Res. 2014; 28 (9): 1275- 1283.
CrossRef Google scholar
[107]
Wang CH , Lin CY , Chen JS , et al. Karnofsky performance status as a predictive factor for cancer-related fatigue treatment with astragalus polysaccharides (PG2) injection-a double blind, multi-center, randomized phase IV study. Cancers. 2019; 11 (2): 128.
CrossRef Google scholar
[108]
Wu J , Yu J , Wang J , et al. Astragalus polysaccharide enhanced antitumor effects of Apatinib in gastric cancer AGS cells by inhibiting AKT signalling pathway. Biomed Pharmacother. 2018; 100: 176- 183.
CrossRef Google scholar
[109]
Bamodu OA , Kuo KT , Wang CH , et al. Astragalus polysaccharides (PG2) Enhances the M1 polarization of macrophages, functional maturation of dendritic cells, and T cell-mediated anticancer immune responses in patients with lung cancer. Nutrients. 2019; 11 (10): 2264.
CrossRef Google scholar
[110]
Yang YL , Lin ZW , He PT , Nie H , Yao QY , Zhang SY . Inhibitory effect of astragalus polysaccharide combined with cisplatin on cell cycle and migration of nasopharyngeal carcinoma cell lines. Biol Pharm Bull. 2021; 44 (7): 926- 931.
CrossRef Google scholar
[111]
Liao CH , Yong CY , Lai GM , et al. Astragalus polysaccharide (PG2) suppresses macrophage migration inhibitory factor and aggressiveness of lung adenocarcinoma cells. Am J Chin Med. 2020; 48 (6): 1491- 1509.
CrossRef Google scholar
[112]
Soumoy L , Ghanem GE , Saussez S , Journe F . Bufalin for an innovative therapeutic approach against cancer. Pharmacol Res. 2022; 184: 106442.
CrossRef Google scholar
[113]
Cheng CS , Wang J , Chen J , et al. New therapeutic aspects of steroidal cardiac glycosides: the anticancer properties of Huachansu and its main active constituent Bufalin. Cancer Cell Int. 2019; 19 (1): 92.
CrossRef Google scholar
[114]
Zou D , Song J , Deng M , et al. Bufalin inhibits peritoneal dissemination of gastric cancer through endothelial nitric oxide synthase-mitogen-activated protein kinases signaling pathway. FASEB J. 2021; 35 (5): e21601.
CrossRef Google scholar
[115]
Yang H , Liu Y , Zhao MM , et al. Therapeutic potential of targeting membrane-spanning proteoglycan SDC4 in hepatocellular carcinoma. Cell Death Dis. 2021; 12 (5): 492.
CrossRef Google scholar
[116]
Qian L , Su H , Wang G , Li B , Shen G , Gao Q . Anti-tumor activity of bufalin by inhibiting c-MET mediated MEK/ERK and PI3K/AKT signaling pathways in gallbladder cancer. J Cancer. 2020; 11 (11): 3114- 3123.
CrossRef Google scholar
[117]
Fang K , Zhan Y , Zhu R , et al. Bufalin suppresses tumour microenvironment-mediated angiogenesis by inhibiting the STAT3 signalling pathway. J Transl Med. 2021; 19 (1): 383.
CrossRef Google scholar
[118]
Wang H , Zhang C , Ning Z , Xu L , Zhu X , Meng Z . Bufalin enhances anti-angiogenic effect of sorafenib via AKT/VEGF signaling. Int J Oncol. 2016; 48 (3): 1229- 1241.
CrossRef Google scholar
[119]
Xie CM , Chan WY , Yu S , Zhao J , Cheng CH . Bufalin induces autophagy-mediated cell death in human colon cancer cells through reactive oxygen species generation and JNK activation. Free Radic Biol Med. 2011; 51 (7): 1365- 1375.
CrossRef Google scholar
[120]
Yin JQ , Shen JN , Su WW , et al. Bufalin induces apoptosis in human osteosarcoma U-2OS and U-2OS methotrexate300-resistant cell lines. Acta Pharmacol Sin. 2007; 28 (5): 712- 720.
CrossRef Google scholar
[121]
Yu CH , Kan SF , Pu HF , Jea Chien E , Wang PS . Apoptotic signaling in bufalin- and cinobufagin-treated androgen-dependent and -independent human prostate cancer cells. Cancer Sci. 2008; 99 (12): 2467- 2476.
CrossRef Google scholar
[122]
Qi F , Inagaki Y , Gao B , et al. Bufalin and cinobufagin induce apoptosis of human hepatocellular carcinoma cells via Fas- and mitochondria-mediated pathways. Cancer Sci. 2011; 102 (5): 951- 958.
CrossRef Google scholar
[123]
Zhu Z , Sun H , Ma G , et al. Bufalin induces lung cancer cell apoptosis via the inhibition of PI3K/Akt pathway. Int J Mol Sci. 2012; 13 (2): 2025- 2035.
CrossRef Google scholar
[124]
Kim NY , Suh YA , Kim S , Lee C . Bufalin down-regulates Axl expression to inhibit cell proliferation and induce apoptosis in non-small-cell lung cancer cells. Biosci Rep. 2020; 40 (4): BSR20193959.
CrossRef Google scholar
[125]
Nguyen HN , Ullevig SL , Short JD , Wang L , Ahn YJ , Asmis R . Ursolic acid and related analogues: triterpenoids with broad health benefits. Antioxidants. 2021; 10 (8): 1161.
CrossRef Google scholar
[126]
Iqbal J , Abbasi BA , Ahmad R , et al. Ursolic acid a promising candidate in the therapeutics of breast cancer: current status and future implications. Biomed Pharmacother. 2018; 108: 752- 756.
CrossRef Google scholar
[127]
López-Hortas L , Pérez-Larrán P , González-Muñoz MJ , Falqué E , Domínguez H . Recent developments on the extraction and application of ursolic acid. Food Res Int. 2018; 103: 130- 149.
CrossRef Google scholar
[128]
Li, J , Dai C , Shen L . Ursolic acid inhibits epithelial-mesenchymal transition through the Axl/NF-κB pathway in gastric cancer cells. Evid Based Complement Alternat Med. 2019; 2019: 2474805.
CrossRef Google scholar
[129]
Goufo P , Singh RK , Cortez I . A reference list of phenolic compounds (including stilbenes) in grapevine (Vitis vinifera L.) roots, woods, canes, stems, and leaves. Antioxidants. 2020; 9 (5): 398.
CrossRef Google scholar
[130]
Liu T , Liu P , Ding F , et al. Ampelopsin reduces the migration and invasion of ovarian cancer cells via inhibition of epithelial-to-mesenchymal transition. Oncol Rep. 2015; 33 (2): 861- 867.
CrossRef Google scholar
[131]
Qi S , Kou X , Lv J , Qi Z , Yan L . Ampelopsin induces apoptosis in HepG2 human hepatoma cell line through extrinsic and intrinsic pathways: involvement of P38 and ERK. Environ Toxicol Pharmacol. 2015; 40 (3): 847- 854.
CrossRef Google scholar
[132]
Zhou Y , Liang X , Chang H , et al. Ampelopsin-induced autophagy protects breast cancer cells from apoptosis through Akt-mTOR pathway via endoplasmic reticulum stress. Cancer Sci. 2014; 105 (10): 1279- 1287.
CrossRef Google scholar
[133]
Huang C , Huang YL , Wang CC , Pan YL , Lai YH , Huang HC . Ampelopsins A and C induce apoptosis and metastasis through downregulating AxL, TYRO3, and FYN expressions in MDA-MB-231 breast cancer cells. J Agric Food Chem. 2019; 67 (10): 2818- 2830.
CrossRef Google scholar
[134]
Shi H , Shi D , Wu Y , Shen Q , Li J . Qigesan inhibits migration and invasion of esophageal cancer cells via inducing connexin expression and enhancing gap junction function. Cancer Lett. 2016; 380 (1): 184- 190.
CrossRef Google scholar
[135]
Kong L , Wu Z , Zhao Y , et al. Qigesan reduces the motility of esophageal cancer cells via inhibiting Gas6/Axl and NF-kappaB expression. Biosci Rep. 2019; 39 (6): BSR20190850.
CrossRef Google scholar
[136]
Kong L , Lu X , Chen X , et al. Qigesan inhibits esophageal cancer cell invasion and migration by inhibiting Gas6/Axl-induced epithelial-mesenchymal transition. Aging (Albany NY). 2020; 12 (10): 9714- 9725.
CrossRef Google scholar
[137]
Yao CJ , Chow JM , Lin PC , et al. Activation of p53/miR-34a tumor suppressor Axis by Chinese herbal formula JP-1 in A549 lung 188-AXL PROMOTES MALIGNANT PHENOTYPESadenocarcinoma cells. Evid Based Complement Alternat Med. 2016; 2016 (1): 5989681.
CrossRef Google scholar
[138]
Zhang J , Hu K , Di L , et al. Traditional herbal medicine and nanomedicine: converging disciplines to improve therapeutic efficacy and human health. Adv Drug Deliv Rev. 2021; 178: 113964.
CrossRef Google scholar
[139]
Xiang YN , Cuo ZM , Zhu PF , Chen J , Huang YY . Traditional Chinese medicine as a cancer treatment: modern perspectives of ancient but advanced science. Cancer Med. 2019; 8 (5): 1958- 1975.
CrossRef Google scholar
[140]
Huang XM , Yang ZJ , Xie Q , Zhang ZK , Zhang H , Ma JY . Natural products for treating colorectal cancer: a mechanistic review. Biomed Pharmacother. 2019; 117: 109142.
CrossRef Google scholar
[141]
Kim A , Ha J , Kim J , et al. Natural products for pancreatic cancer treatment: from traditional medicine to modern drug discovery. Nutrients. 2021; 13 (11): 3801.
CrossRef Google scholar

RIGHTS & PERMISSIONS

2025 The Author(s). Advanced Chinese Medicine published by John Wiley & Sons Australia, Ltd on behalf of Higher Education Press.
AI Summary AI Mindmap
PDF(885 KB)

Accesses

Citations

Detail

Sections
Recommended

/