Research advances in natural sesquiterpene lactones: overcoming cancer drug resistance through modulation of key signaling pathways

Chi Teng , Jia-Wen Chen , Li-Sha Shen , Sibao Chen , Guo-Qing Chen

Cancer Drug Resistance ›› 2025, Vol. 8 : 13

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Cancer Drug Resistance ›› 2025, Vol. 8 :13 DOI: 10.20517/cdr.2024.178
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Research advances in natural sesquiterpene lactones: overcoming cancer drug resistance through modulation of key signaling pathways

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Abstract

Cancer remains a significant global health challenge, with current chemotherapeutic strategies frequently limited by the emergence of resistance. In this context, natural compounds with the potential to overcome resistance have garnered considerable attention. Among these, sesquiterpene lactones, primarily derived from plants in the Asteraceae family, stand out for their potential anticancer properties. This review specifically focuses on five key signaling pathways: PI3K/Akt/mTOR, NF-κB, Wnt/β-catenin, MAPK/ERK, and STAT3, which play central roles in the mechanisms of cancer resistance. For each of these pathways, we detail their involvement in both cancer development and the emergence of drug resistance. Additionally, we investigate how sesquiterpene lactones modulate these pathways to overcome resistance across diverse cancer types. These insights highlight the potential of sesquiterpene lactones to drive the advancement of novel therapies that can effectively combat both cancer progression and drug resistance.

Keywords

Sesquiterpene lactone / natural product / anticancer / drug resistance

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Chi Teng, Jia-Wen Chen, Li-Sha Shen, Sibao Chen, Guo-Qing Chen. Research advances in natural sesquiterpene lactones: overcoming cancer drug resistance through modulation of key signaling pathways. Cancer Drug Resistance, 2025, 8: 13 DOI:10.20517/cdr.2024.178

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References

[1]

Ferlay J,Soerjomataram I.Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods.Int J Cancer2019;144:1941-53

[2]

Miller KD,Devasia T.Cancer treatment and survivorship statistics, 2022.CA Cancer J Clin2022;72:409-36

[3]

Cragg GM,Newman DJ.Impact of natural products on developing new anti-cancer agents.Chem Rev2009;109:3012-43

[4]

Naeem A,Yang M.Natural products as anticancer agents: current status and future perspectives.Molecules2022;27:8367 PMCID:PMC9737905

[5]

Seaman FC.Sesquiterpene lactones as taxonomic characters in the asteraceae.Bot Rev1982;48:121-594

[6]

Schmidt TJ.Structure-activity relationships of sesquiterpene lactones.Stud Nat Prod Chem2006;33:309-92

[7]

Babaei G,Abroon S,Aziz SG.Application of sesquiterpene lactone: a new promising way for cancer therapy based on anticancer activity.Biomed Pharmacother2018;106:239-46

[8]

Krishna S,Ster IC.A randomised, double blind, placebo-controlled pilot study of oral artesunate therapy for colorectal cancer.EBioMedicine2015;2:82-90 PMCID:PMC4484515

[9]

Curry EA 3rd,Yoder C.Phase I dose escalation trial of feverfew with standardized doses of parthenolide in patients with cancer.Invest New Drugs2004;22:299-305

[10]

Efferth T.From ancient herb to modern drug: artemisia annua and artemisinin for cancer therapy.Semin Cancer Biol2017;46:65-83

[11]

Liu Y,Cheng F.Xanthatin induce DDP-resistance lung cancer cells apoptosis through regulation of GLUT1 mediated ROS accumulation.Drug Dev Res2023;84:1266-78

[12]

Chen J,Zou Z.Costunolide enhances doxorubicin-induced apoptosis in prostate cancer cells via activated mitogen-activated protein kinases and generation of reactive oxygen species.Oncotarget2017;8:107701-15 PMCID:PMC5746101

[13]

Xu Z,Sun S.Mecheliolide elicits ROS-mediated ERS driven immunogenic cell death in hepatocellular carcinoma.Redox Biol2022;54:102351 PMCID:PMC9168183

[14]

Chun J,Lee M,Jeong MK.The sesquiterpene lactone-rich fraction of Inula helenium L. enhances the antitumor effect of anti-PD-1 antibody in colorectal cancer: integrative phytochemical, transcriptomic, and experimental analyses.Cancers2023;15:653 PMCID:PMC9913754

[15]

Mangalpady SS,Borbolla-Jiménez F.Arnicolide D: a multi-targeted anticancer sesquiterpene lactone-preclinical efficacy and mechanistic insights.Naunyn Schmiedebergs Arch Pharmacol2024;397:6317-36

[16]

Liu X.Recent advances on the structural modification of parthenolide and its derivatives as anticancer agents.Chin J Nat Med2022;20:814-29

[17]

Gao Y,Cao H.Scabertopin derived from Elephantopus Scaber L. mediates necroptosis by inducing reactive oxygen species production in bladder cancer in vitro.Cancers2022;14:5976 PMCID:PMC9738305

[18]

Tu Y.Artemisinin-A gift from traditional Chinese medicine to the world (Nobel Lecture).Angew Chem Int Ed Engl2016;55:10210-26

[19]

Balint GA.Artemisinin and its derivatives: an important new class of antimalarial agents.Pharmacol Ther2001;90:261-5

[20]

Liu C.Discovery and development of artemisinin and related compounds.Chin Herb Med2017;9:101-14

[21]

Tiwari MK.Artemisinin-derived antimalarial endoperoxides from bench-side to bed-side: chronological advancements and future challenges.Med Res Rev2020;40:1220-75

[22]

Li Y.Qinghaosu (artemisinin): chemistry and pharmacology.Acta Pharmacol Sin2012;33:1141-6 PMCID:PMC4003104

[23]

Zeng ZW,Chen L,Li Y.A comprehensive overview of Artemisinin and its derivatives as anticancer agents.Eur J Med Chem2023;247:115000

[24]

Jia J,Zhang L.Artemisinin inhibits gallbladder cancer cell lines through triggering cell cycle arrest and apoptosis.Mol Med Rep2016;13:4461-8

[25]

Li B,Sun J,Lai D.Artemisinin derivatives inhibit epithelial ovarian cancer cells via autophagy-mediated cell cycle arrest.Acta Biochim Biophys Sin2018;50:1227-35

[26]

Wang D,Li Y.Dihydroartemisinin increases apoptosis of colon cancer cells through targeting Janus kinase 2/signal transducer and activator of transcription 3 signaling.Oncol Lett2018;15:1949-54 PMCID:PMC5776939

[27]

Cui YQ,Zhang F.The suppressive effects of Britannin (Bri) on human liver cancer through inducing apoptosis and autophagy via AMPK activation regulated by ROS.Biochem Biophys Res Commun2018;497:916-23

[28]

Chen Y,Wu P.Artesunate induces apoptosis, autophagy and ferroptosis in diffuse large B cell lymphoma cells by impairing STAT3 signaling.Cell Signal2021;88:110167

[29]

Beccafico S,Marchetti MC.Artesunate induces ROS- and p38 MAPK-mediated apoptosis and counteracts tumor growth in vivo in embryonal rhabdomyosarcoma cells.Carcinogenesis2015;36:1071-83

[30]

Zhou X,Wang F.Artesunate induces autophagy dependent apoptosis through upregulating ROS and activating AMPK-mTOR-ULK1 axis in human bladder cancer cells.Chem Biol Interact2020;331:109273

[31]

Konishi T,Nagao T,Konoshima T.Antiproliferative sesquiterpene lactones from the roots of Inula helenium.Biol Pharm Bull2002;25:1370-2

[32]

Tepkeeva II,Zborovskaya IB.Cytostatic activity of peptide extracts of medicinal plants on transformed A549, H1299, and HeLa Cells.Bull Exp Biol Med2009;147:48-51

[33]

O'Shea S,Cotter L.In vitro activity of Inula helenium against clinical Staphylococcus aureus strains including MRSA.Br J Biomed Sci2009;66:186-9

[34]

Cantrell CL,Fronczek FR,Quijano L.Antimycobacterial eudesmanolides from Inula helenium and Rudbeckia subtomentosa.Planta Med1999;65:351-5

[35]

Zhao F,He EQ,Liu K.Inhibitory effects of sesquiterpenes from Saussurea lappa on the overproduction of nitric oxide and TNF-alpha release in LPS-activated macrophages.J Asian Nat Prod Res2008;10:1045-53

[36]

Chen J,Huang R.Alantolactone inhibits oesophageal adenocarcinoma cells through nuclear factor erythroid 2-related factor 2-mediated reactive oxygen species increment.Basic Clin Pharmacol Toxicol2023;132:253-62

[37]

Ren Y,Zhang J.Alantolactone exhibits antiproliferative and apoptosis-promoting properties in colon cancer model via activation of the MAPK-JNK/c-Jun signaling pathway.Mol Cell Biochem2021;476:4387-403

[38]

Yin C,Huang X.Alantolactone promotes ER stress-mediated apoptosis by inhibition of TrxR1 in triple-negative breast cancer cell lines and in a mouse model.J Cell Mol Med2019;23:2194-206 PMCID:PMC6378194

[39]

Kim MY,Ji SY.Induction of apoptosis by isoalantolactone in human hepatocellular carcinoma Hep3B cells through activation of the ROS-dependent JNK signaling pathway.Pharmaceutics2021;13:1627 PMCID:PMC8540929

[40]

Li J,Chen Y.Isoalantolactone induces cell cycle arrest, apoptosis and autophagy in colorectal cancer cells.Front Pharmacol2022;13:903599 PMCID:PMC9133875

[41]

Zhang C,Xiong J.Isoalantolactone inhibits pancreatic cancer proliferation by regulation of PI3K and Wnt signal pathway.PLoS One2021;16:e0247752 PMCID:PMC7932101

[42]

Lee SH,Lim JS.Costunolide, a sesquiterpene lactone, suppresses skin cancer via induction of apoptosis and blockage of cell proliferation.Int J Mol Sci2021;22:2075 PMCID:PMC7922093

[43]

Xu C,Lei X.Costunolide-induced apoptosis via promoting the reactive oxygen species and inhibiting AKT/GSK3β pathway and activating autophagy in gastric cancer.Front Cell Dev Biol2021;9:722734 PMCID:PMC8633576

[44]

Zhuge W,Vladimir K.Costunolide specifically binds and inhibits thioredoxin reductase 1 to induce apoptosis in colon cancer.Cancer Lett2018;412:46-58

[45]

Peng Y,Wang S,Li X.Dehydrocostus lactone inhibits the proliferation of esophageal cancer cells in vivo and in vitro through ROS-mediated apoptosis and autophagy.Food Chem Toxicol2022;170:113453

[46]

Lee KH,Wolo MT.Antitumor agents. XV: deoxyelephantopin, an antitumor principle from Elephantopus carolinianus Willd.J Pharm Sci1975;64:1572-3

[47]

Mehmood T.Deoxyelephantopin and its isomer isodeoxyelephantopin: anti-cancer natural products with multiple modes of action.Molecules2022;27:2086 PMCID:PMC9000713

[48]

Bai M,Xu W.Elephantopinolide A-P, germacrane-type sesquiterpene lactones from Elephantopus scaber induce apoptosis, autophagy and G2/M phase arrest in hepatocellular carcinoma cells.Eur J Med Chem2020;198:112362

[49]

Kabeer FA,Nair MS.Molecular mechanisms of anticancer activity of deoxyelephantopin in cancer cells.Integr Med Res2017;6:190-206 PMCID:PMC5478298

[50]

Hong L,Wu F.Isodeoxyelephantopin inactivates thioredoxin reductase 1 and activates ROS-mediated JNK signaling pathway to exacerbate cisplatin effectiveness in human colon cancer cells.Front Cell Dev Biol2020;8:580517 PMCID:PMC7536313

[51]

Verma SS,Awasthee N.Isodeoxyelephantopin, a sesquiterpene lactone induces ROS generation, suppresses NF-κB activation, modulates LncRNA expression and exhibit activities against breast cancer.Sci Rep2019;9:17980 PMCID:PMC6884568

[52]

Feng JH,Lee KH.A novel plant sesquiterpene lactone derivative, DETD-35, suppresses BRAFV600E mutant melanoma growth and overcomes acquired vemurafenib resistance in mice.Mol Cancer Ther2016;15:1163-76 PMCID:PMC4893919

[53]

Nakagawa-Goto K,Cheng YT.Novel sesquiterpene lactone analogues as potent anti-breast cancer agents.Mol Oncol2016;10:921-37 PMCID:PMC5152578

[54]

Cvetanova B,Yang CC.Sesquiterpene lactone deoxyelephantopin isolated from Elephantopus scaber and its derivative DETD-35 suppress BRAFV600E mutant melanoma lung metastasis in mice.Int J Mol Sci2021;22:3226 PMCID:PMC8004649

[55]

Yan QL,Bai M,Song SJ.Sesquiterpene lactones from Elephantopus scaber exhibit cytotoxic effects on glioma cells by targeting GSTP1.Bioorg Chem2022;129:106183

[56]

Wiedhopf RM,Bianchi E.Tumor inhibitory agent from Magnolia grandiflora (Magnoliaceae). I. Parthenolide.J Pharm Sci1973;62:345

[57]

Ghantous A,Herceg Z.Parthenolide: from plant shoots to cancer roots.Drug Discov Today2013;18:894-905

[58]

Woods JR,Bieberich AA,Colby DA.Amino-derivatives of the sesquiterpene lactone class of natural products as prodrugs.Med Chem Commun2013;4:27-33

[59]

Dong Y,Li J.Sesquiterpene lactones and cancer: new insight into antitumor and anti-inflammatory effects of parthenolide-derived dimethylaminomicheliolide and micheliolide.Comput Math Methods Med2022;2022:3744837 PMCID:PMC9313921

[60]

Jin P,Augsburger LL.The solution and solid state stability and excipient compatibility of parthenolide in feverfew.AAPS PharmSciTech2007;8:E105 PMCID:PMC2750358

[61]

Peng F,Li S.Correction: Micheliolide ameliorates renal fibrosis by suppressing the Mtdh/BMP/MAPK pathway.Lab Invest2020;100:786-7 PMCID:PMC7609261

[62]

Zhu J,Yu Z.Epoxymicheliolide, a novelguaiane-type sesquiterpene lactone, inhibits NF‑κB/COX‑2 signaling pathways by targeting leucine 281 and leucine 25 in IKKβ in renal cell carcinoma.Int J Oncol2018;53:987-1000 PMCID:PMC6065450

[63]

Jhanwar-Uniyal M,Mohan AL.Diverse signaling mechanisms of mTOR complexes: mTORC1 and mTORC2 in forming a formidable relationship.Adv Biol Regul2019;72:51-62

[64]

Viennois E,Ayyadurai S.Micheliolide, a new sesquiterpene lactone that inhibits intestinal inflammation and colitis-associated cancer.Lab Invest2014;94:950-65

[65]

Karam L,Chaaban R.Anticancer activities of parthenolide in primary effusion lymphoma preclinical models.Mol Carcinog2021;60:567-81

[66]

Li H,Lv M,Sun Y.Parthenolide facilitates apoptosis and reverses drug-resistance of human gastric carcinoma cells by inhibiting the STAT3 signaling pathway.Oncol Lett2018;15:3572-9 PMCID:PMC5796286

[67]

Sun L,Wen G.Parthenolide inhibits human lung cancer cell growth by modulating the IGF‑1R/PI3K/Akt signaling pathway.Oncol Rep2020;44:1184-93

[68]

Duan D,Yao J,Fang J.Targeting thioredoxin reductase by parthenolide contributes to inducing apoptosis of HeLa cells.J Biol Chem2016;291:10021-31 PMCID:PMC4858956

[69]

Liu W,Sun J,Li W.Parthenolide suppresses pancreatic cell growth by autophagy-mediated apoptosis.Onco Targets Ther2017;10:453-61 PMCID:PMC5271392

[70]

Tang X,Chen C.Micheliolide inhibits gastric cancer growth in vitro and in vivo via blockade of the IL-6/STAT3 pathway.Pharmazie2019;74:175-8

[71]

Feng D,Liu Y.Micheliolide suppresses the viability, migration and invasion of U251MG cells via the NF-κB signaling pathway.Oncol Lett2020;20:67 PMCID:PMC7436293

[72]

Zhang S,Ba G.Antitumor effects of the small molecule DMAMCL in neuroblastoma via suppressing aerobic glycolysis and targeting PFKL.Cancer Cell Int2021;21:619 PMCID:PMC8613996

[73]

Yao S,Yin M.DMAMCL exerts antitumor effects on hepatocellular carcinoma both in vitro and in vivo.Cancer Lett2020;483:87-97

[74]

Wang Y,Yang Y.ROS generation and autophagosome accumulation contribute to the DMAMCL-induced inhibition of glioma cell proliferation by regulating the ROS/MAPK signaling pathway and suppressing the Akt/mTOR signaling pathway.Onco Targets Ther2019;12:1867-80 PMCID:PMC6413739

[75]

Johansson MH.Reversible Michael additions: covalent inhibitors and prodrugs.Mini Rev Med Chem2012;12:1330-44

[76]

Liu YQ.Promising anticancer activities and mechanisms of action of active compounds from the medicinal herb Centipeda minima (L.) A. Braun & Asch.Phytomedicine2022;106:154397

[77]

Liu R,Mok DK,Tai WC.Arnicolide D, from the herb Centipeda minima, is a therapeutic candidate against nasopharyngeal carcinoma.Molecules2019;24:1908 PMCID:PMC6571971

[78]

Qu Z,Mok DK,Tai WC.Arnicolide D inhibits triple negative breast cancer cell proliferation by suppression of Akt/mTOR and STAT3 signaling pathways.Int J Med Sci2020;17:1482-90 PMCID:PMC7359397

[79]

Zhu P,Fu X.Arnicolide D exerts anti-melanoma effects and inhibits the NF-κB pathway.Phytomedicine2019;64:153065

[80]

Lin YS,Shen LS.Arnicolide D induces endoplasmic reticulum stress-mediated oncosis via ATF4 and CHOP in hepatocellular carcinoma cells.Cell Death Discov2024;10:134 PMCID:PMC10933425

[81]

Tan Z,Chen X.Ellagic acid inhibits tumor growth and potentiates the therapeutic efficacy of sorafenib in hepatocellular carcinoma.Heliyon2024;10:e23931 PMCID:PMC10777069

[82]

Su T,Wang XN.The JAK2/STAT3 pathway is involved in the anti-melanoma effects of brevilin A.Life Sci2020;241:117169

[83]

Liu R,Lin Y,Tai WC.Brevilin A induces cell cycle arrest and apoptosis in nasopharyngeal carcinoma.Front Pharmacol2019;10:594 PMCID:PMC6544084

[84]

Saleem MZ,Alshwmi M.Brevilin A inhibits STAT3 signaling and induces ROS-dependent apoptosis, mitochondrial stress and endoplasmic reticulum stress in MCF-7 breast cancer cells.Onco Targets Ther2020;13:435-50 PMCID:PMC6970270

[85]

You P,Deng M,Li F.Brevilin A induces apoptosis and autophagy of colon adenocarcinoma cell CT26 via mitochondrial pathway and PI3K/AKT/mTOR inactivation.Biomed Pharmacother2018;98:619-25

[86]

Bailly C.Anticancer targets and signaling pathways activated by britannin and related pseudoguaianolide sesquiterpene lactones.Biomedicines2021;9:1325 PMCID:PMC8533303

[87]

Seca AM,Pinto DC.The genus Inula and their metabolites: from ethnopharmacological to medicinal uses.J Ethnopharmacol2014;154:286-310

[88]

Zhang YF,Li MY.Britannin stabilizes T cell activity and inhibits proliferation and angiogenesis by targeting PD-L1 via abrogation of the crosstalk between Myc and HIF-1α in cancer.Phytomedicine2021;81:153425

[89]

Deng M,Long J,Xie L.Atractylenolides (I, II, and III): a review of their pharmacology and pharmacokinetics.Arch Pharm Res2021;44:633-54

[90]

Wang K,Sang X.Atractylenolide I inhibits colorectal cancer cell proliferation by affecting metabolism and stemness via AKT/mTOR signaling.Phytomedicine2020;68:153191

[91]

Wang J,Adlat S,Jiang N.Atractylenolide II induces apoptosis of prostate cancer cells through regulation of AR and JAK2/STAT3 signaling pathways.Molecules2018;23:3298 PMCID:PMC6320989

[92]

Cho IJ,Kim EO.Hemistepsin a induces apoptosis of hepatocellular carcinoma cells by downregulating STAT3.Int J Mol Sci2021;22:4743 PMCID:PMC8125382

[93]

Kim KY,Yeom SH.Inhibition of autophagy promotes hemistepsin A-induced apoptosis via reactive oxygen species-mediated AMPK-dependent signaling in human prostate cancer cells.Biomolecules2021;11:1806 PMCID:PMC8699411

[94]

Wang L,Li F.Cytotoxic sesquiterpene lactones from aerial parts of Xanthium sibiricum.Planta Med2013;79:661-5

[95]

Chen H,Huang X.Xanthatin suppresses proliferation and tumorigenicity of glioma cells through autophagy inhibition via activation of the PI3K-Akt-mTOR pathway.Pharmacol Res Perspect2023;11:e01041 PMCID:PMC9792428

[96]

Shi TL,Cheng QY.Xanthatin induces apoptosis by activating endoplasmic reticulum stress in hepatoma cells.Eur J Pharmacol2019;843:1-11

[97]

Miranda MA,Torres A,Gualtieri SC.Phytotoxins from Tithonia diversifolia.J Nat Prod2015;78:1083-92

[98]

Wei R,Wang J.Tagitinin C induces ferroptosis through PERK-Nrf2-HO-1 signaling pathway in colorectal cancer cells.Int J Biol Sci2021;17:2703-17 PMCID:PMC8326123

[99]

Andersen TB,Manczak T,Simonsen HT.Thapsigargin - from Thapsia L. to mipsagargin.Molecules2015;20:6113-27 PMCID:PMC6272310

[100]

Huang F,Wang X.Thapsigargin induces apoptosis of prostate cancer through cofilin-1 and paxillin.Oncol Lett2018;16:1975-80 PMCID:PMC6036437

[101]

Wu L,Kuang Y,Deng X.Thapsigargin induces apoptosis in adrenocortical carcinoma by activating endoplasmic reticulum stress and the JNK signaling pathway: an in vitro and in vivo study.Drug Des Devel Ther2019;13:2787-98 PMCID:PMC6697672

[102]

Chen JH,Tzeng DTW,Tzeng YM.Antrocin, a bioactive component from Antrodia cinnamomea, suppresses breast carcinogenesis and stemness via downregulation of β-catenin/Notch1/Akt signaling.Phytomedicine2019;52:70-8

[103]

Chiu KY,Chia CH,Tzeng YM.Inhibition of growth, migration and invasion of human bladder cancer cells by antrocin, a sesquiterpene lactone isolated from Antrodia cinnamomea, and its molecular mechanisms.Cancer Lett2016;373:174-84

[104]

Roozbehani M,Hamzeloo-Moghadam M,Fallahian F.Gaillardin, a potent sesquiterpene lactone induces apoptosis via down-regulation of NF-κβ in gastric cancer cells, AGS and MKN45.J Ethnopharmacol2021;281:114529

[105]

Engelman JA.Targeting PI3K signalling in cancer: opportunities, challenges and limitations.Nat Rev Cancer2009;9:550-62

[106]

Dong C,Chen Y,Chen C.Activation of PI3K/AKT/mTOR pathway causes drug resistance in breast cancer.Front Pharmacol2021;12:628690 PMCID:PMC8005514

[107]

Tian LY,Jücker M.The role of PI3K/AKT/mTOR signaling in hepatocellular carcinoma metabolism.Int J Mol Sci2023;24:2652 PMCID:PMC9916527

[108]

Song M,Dong Z.AKT as a therapeutic target for cancer.Cancer Res2019;79:1019-31

[109]

Nicholson KM.The protein kinase B/Akt signalling pathway in human malignancy.Cell Signal2002;14:381-95

[110]

Hua H,Zhang H,Luo T.Targeting mTOR for cancer therapy.J Hematol Oncol2019;12:71 PMCID:PMC6612215

[111]

Zou Z,Li H.mTOR signaling pathway and mTOR inhibitors in cancer: progress and challenges.Cell Biosci2020;10:31 PMCID:PMC7063815

[112]

Mafi S,Taeb S.mTOR-mediated regulation of immune responses in cancer and tumor microenvironment.Front Immunol2021;12:774103 PMCID:PMC8894239

[113]

Burris HA 3rd.Overcoming acquired resistance to anticancer therapy: focus on the PI3K/AKT/mTOR pathway.Cancer Chemother Pharmacol2013;71:829-42

[114]

Murugan AK.mTOR: role in cancer, metastasis and drug resistance.Semin Cancer Biol2019;59:92-111

[115]

Chen MY,Setiawan SA.Ovatodiolide and antrocin synergistically inhibit the stemness and metastatic potential of hepatocellular carcinoma via impairing ribosome biogenesis and modulating ERK/Akt-mTOR signaling axis.Phytomedicine2023;108:154478

[116]

Jing W,Yingru X.Artesunate promotes sensitivity to sorafenib in hepatocellular carcinoma.Biochem Biophys Res Commun2019;519:41-5

[117]

Wang Y,Liu L,Li H.Effects of artemisinin combined with 5-fluorouracil on colon cancer cell proliferation, migration, and drug sensitivity via PI3K/AKT signaling.J Biomater Tissue Eng2020;10:1600-4

[118]

Brotelle T.[PI3K-AKT-mTOR pathway: Description, therapeutic development, resistance, predictive/prognostic biomarkers and therapeutic applications for cancer].Bull Cancer2016;103:18-29

[119]

Liu R,Liu G.PI3K/AKT pathway as a key link modulates the multidrug resistance of cancers.Cell Death Dis2020;11:797 PMCID:PMC7515865

[120]

Gottesman MM,Bates SE.Multidrug resistance in cancer: role of ATP-dependent transporters.Nat Rev Cancer2002;2:48-58

[121]

Cai H,Jiang J,Yang C.Costunolide enhances sensitivity of K562/ADR chronic myeloid leukemia cells to doxorubicin through PI3K/Akt pathway.Phytother Res2019;33:1683-8

[122]

Zhang S,Yuan F.The therapeutic effects of dihydroartemisinin on cisplatin-resistant gastric cancer cells.Curr Pharm Biotechnol2022;23:276-86

[123]

Xu J,Wei WZ.Activation of the Akt survival pathway contributes to TRAIL resistance in cancer cells.PLoS One2010;5:e10226 PMCID:PMC2856686

[124]

Zhang L.Mechanisms of resistance to TRAIL-induced apoptosis in cancer.Cancer Gene Ther2005;12:228-37

[125]

Thanaketpaisarn O,Sakurai H.Artesunate enhances TRAIL-induced apoptosis in human cervical carcinoma cells through inhibition of the NF-κB and PI3K/Akt signaling pathways.Int J Oncol2011;39:279-85

[126]

Hayden MS.NF-κB in immunobiology.Cell Res2011;21:223-44 PMCID:PMC3193440

[127]

Erstad DJ.Targeting the NF-κB pathway in cancer therapy.Surg Oncol Clin N Am2013;22:705-46

[128]

Lin Y,Chen W.The NF-kappaB activation pathways, emerging molecular targets for cancer prevention and therapy.Expert Opin Ther Targets2010;14:45-55 PMCID:PMC3043547

[129]

Yu H,Zhang Z,Hu H.Targeting NF-κB pathway for the therapy of diseases: mechanism and clinical study.Signal Transduct Target Ther2020;5:209 PMCID:PMC7506548

[130]

Hoesel B.The complexity of NF-κB signaling in inflammation and cancer.Mol Cancer2013;12:86 PMCID:PMC3750319

[131]

Li Y,Peng J.Inhibition of NF-κB signaling unveils novel strategies to overcome drug resistance in cancers.Drug Resist Updat2024;73:101042

[132]

Wei W,Zhao S.Alantolactone induces apoptosis in chronic myelogenous leukemia sensitive or resistant to imatinib through NF-κB inhibition and Bcr/Abl protein deletion.Apoptosis2013;18:1060-70

[133]

Fang LJ,Wang S,Xu T.Sesquiterpene lactone parthenolide markedly enhances sensitivity of human A549 cells to low-dose oxaliplatin via inhibition of NF-kappaB activation and induction of apoptosis.Planta Med2010;76:258-64

[134]

Zhang Z,Zhao H.Gemcitabine treatment promotes pancreatic cancer stemness through the Nox/ROS/NF-κB/STAT3 signaling cascade.Cancer Lett2016;382:53-63

[135]

Ji D,Huang P.Deoxyelephantopin induces apoptosis via oxidative stress and enhances gemcitabine sensitivity in vitro and in vivo through targeting the NF-κB signaling pathway in pancreatic cancer.Aging2020;12:11116-38 PMCID:PMC7346037

[136]

Holcomb BK,Waters JA,Crooks PA.Dimethylamino parthenolide enhances the inhibitory effects of gemcitabine in human pancreatic cancer cells.J Gastrointest Surg2012;16:1333-40

[137]

Ho EA.Regulation of multidrug resistance by pro-inflammatory cytokines.Curr Cancer Drug Targets2006;6:295-311

[138]

Li Q,Cheng J.Dihydroartemisinin as a sensitizing agent in cancer therapies.Onco Targets Ther2021;14:2563-73 PMCID:PMC8053502

[139]

Dolcet X,Pallares J.NF-kB in development and progression of human cancer.Virchows Arch2005;446:475-82

[140]

Khongthong P,Edwards J.The NF-KB pathway and endocrine therapy resistance in breast cancer.Endocr Relat Cancer2019;26:R369-80

[141]

Gyrd-Hansen M.IAPs: from caspase inhibitors to modulators of NF-kappaB, inflammation and cancer.Nat Rev Cancer2010;10:561-74

[142]

MacDonald BT,He X.Wnt/beta-catenin signaling: components, mechanisms, and diseases.Dev Cell2009;17:9-26 PMCID:PMC2861485

[143]

Clevers H.Wnt/beta-catenin signaling in development and disease.Cell2006;127:469-80

[144]

Arend RC,Straughn JM Jr.The Wnt/β-catenin pathway in ovarian cancer: a review.Gynecol Oncol2013;131:772-9

[145]

Kolligs FT,Göke B.Wnt/beta-catenin/tcf signaling: a critical pathway in gastrointestinal tumorigenesis.Digestion2002;66:131-44

[146]

Zhang Y.Targeting the Wnt/β-catenin signaling pathway in cancer.J Hematol Oncol2020;13:165 PMCID:PMC7716495

[147]

Krishnamurthy N.Targeting the Wnt/beta-catenin pathway in cancer: Update on effectors and inhibitors.Cancer Treat Rev2018;62:50-60 PMCID:PMC5745276

[148]

Lorzadeh S,Ghavami S.Autophagy and the Wnt signaling pathway: a focus on Wnt/β-catenin signaling.Biochim Biophys Acta Mol Cell Res2021;1868:118926

[149]

Rodgers SJ,Oorschot VMJ.INPP4B promotes PI3Kα-dependent late endosome formation and Wnt/β-catenin signaling in breast cancer.Nat Commun2021;12:3140 PMCID:PMC8149851

[150]

Perry JM,Roy A.Overcoming Wnt-β-catenin dependent anticancer therapy resistance in leukaemia stem cells.Nat Cell Biol2020;22:689-700 PMCID:PMC8010717

[151]

Spaan I,van de Stolpe A.Wnt signaling in multiple myeloma: a central player in disease with therapeutic potential.J Hematol Oncol2018;11:67 PMCID:PMC5960217

[152]

Cai W,Luo Q.PMP22 regulates self-renewal and chemoresistance of gastric cancer cells.Mol Cancer Ther2017;16:1187-98

[153]

Ismail M,Li Y.Targeted liposomes for combined delivery of artesunate and temozolomide to resistant glioblastoma.Biomaterials2022;287:121608

[154]

Wang T,Ren W,Cheng YF.Combination treatment with artemisinin and oxaliplatin inhibits tumorigenesis in esophageal cancer EC109 cell through Wnt/β-catenin signaling pathway.Thorac Cancer2020;11:2316-24 PMCID:PMC7396387

[155]

Law SM.Premise and peril of Wnt signaling activation through GSK-3β inhibition.iScience2022;25:104159 PMCID:PMC9010644

[156]

Dai X,Qiao Y.Dihydroartemisinin inhibits the development of colorectal cancer by GSK-3β/TCF7/MMP9 pathway and synergies with capecitabine.Cancer Lett2024;582:216596

[157]

Koni M,Brizzi MF.The Wnt signalling pathway: a tailored target in cancer.Int J Mol Sci2020;21:7697 PMCID:PMC7589708

[158]

Burotto M,Lee JM.The MAPK pathway across different malignancies: a new perspective.Cancer2014;120:3446-56 PMCID:PMC4221543

[159]

Sun Y,Liu T,Yang N.Signaling pathway of MAPK/ERK in cell proliferation, differentiation, migration, senescence and apoptosis.J Recept Signal Transduct Res2015;35:600-4

[160]

De Luca A, Maiello MR, D’Alessio A, Pergameno M, Normanno N. The RAS/RAF/MEK/ERK and the PI3K/AKT signalling pathways: role in cancer pathogenesis and implications for therapeutic approaches.Expert Opin Ther Targets2012;16 Suppl 2:S17-27

[161]

Guo YJ,Liu SB,Xu Y.ERK/MAPK signalling pathway and tumorigenesis.Exp Ther Med2020;19:1997-2007 PMCID:PMC7027163

[162]

Roberts PJ.Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer.Oncogene2007;26:3291-310

[163]

Murphy LO.MAPK signal specificity: the right place at the right time.Trends Biochem Sci2006;31:268-75

[164]

Yang SH,Whitmarsh AJ.MAP kinase signalling cascades and transcriptional regulation.Gene2013;513:1-13

[165]

Deschênes-Simard X,Bourdeau V.Tumor suppressor activity of the ERK/MAPK pathway by promoting selective protein degradation.Genes Dev2013;27:900-15 PMCID:PMC3650227

[166]

Santarpia L,El-Naggar AK.Targeting the MAPK-RAS-RAF signaling pathway in cancer therapy.Expert Opin Ther Targets2012;16:103-19 PMCID:PMC3457779

[167]

Bahar ME,Kim DR.Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies.Signal Transduct Target Ther2023;8:455 PMCID:PMC10725898

[168]

Healy FM,MacEwan DJ.The importance of Ras in drug resistance in cancer.Br J Pharmacol2022;179:2844-67

[169]

Tian X,Gu T.Costunolide is a dual inhibitor of MEK1 and AKT1/2 that overcomes osimertinib resistance in lung cancer.Mol Cancer2022;21:193 PMCID:PMC9535870

[170]

Lee S,Kolch W.Targeting MAPK signaling in cancer: mechanisms of drug resistance and sensitivity.Int J Mol Sci2020;21:1102 PMCID:PMC7037308

[171]

Li X,Liu Y.Preclinical efficacy and safety assessment of artemisinin-chemotherapeutic agent conjugates for ovarian cancer.EBioMedicine2016;14:44-54 PMCID:PMC5161434

[172]

Li S,Wang F.PD-1/PD-L1 interaction upregulates YAP1 expression in HepG2 cells through MAPK/ERK pathway.Nat Prod Commun2023;18:1934578X231210413

[173]

Lee DY,Lee HJ.ERK1/2 activation attenuates TRAIL-induced apoptosis through the regulation of mitochondria-dependent pathway.Toxicol In Vitro2006;20:816-23

[174]

Bromberg JF,Devgan G.Stat3 as an oncogene.Cell1999;98:295-303

[175]

Yu H,Herrmann A,Jove R.Revisiting STAT3 signalling in cancer: new and unexpected biological functions.Nat Rev Cancer2014;14:736-46

[176]

Ma JH,Li X.Role of STAT3 signaling pathway in breast cancer.Cell Commun Signal2020;18:33 PMCID:PMC7048131

[177]

Wang HQ,Huo FY.STAT3 pathway in cancers: past, present, and future.MedComm2022;3:e124 PMCID:PMC8942302

[178]

Horvath CM,Darnell JE Jr.A STAT protein domain that determines DNA sequence recognition suggests a novel DNA-binding domain.Genes Dev1995;9:984-94

[179]

Bromberg J.The role of STATs in transcriptional control and their impact on cellular function.Oncogene2000;19:2468-73

[180]

Courapied S,de Carné Trécesson S.The cdk5 kinase regulates the STAT3 transcription factor to prevent DNA damage upon topoisomerase I inhibition.J Biol Chem2010;285:26765-78 PMCID:PMC2930675

[181]

Fukada T,Yamanaka Y.Two signals are necessary for cell proliferation induced by a cytokine receptor gp130: involvement of STAT3 in anti-apoptosis.Immunity1996;5:449-60

[182]

You L,Li H.The role of STAT3 in autophagy.Autophagy2015;11:729-39 PMCID:PMC4509450

[183]

Hu Y,Liu K.Unraveling the complexity of STAT3 in cancer: molecular understanding and drug discovery.J Exp Clin Cancer Res2024;43:23 PMCID:PMC10799433

[184]

Yu H,Jove R.STATs in cancer inflammation and immunity: a leading role for STAT3.Nat Rev Cancer2009;9:798-809 PMCID:PMC4856025

[185]

Chun J,Cheng MS.Alantolactone selectively suppresses STAT3 activation and exhibits potent anticancer activity in MDA-MB-231 cells.Cancer Lett2015;357:393-403

[186]

Su Q,Luo X,Li H.Artesunate reverses cytarabine resistance in acute myeloid leukemia by blocking the JAK/STAT3 signaling.Hematology2023;28:2255802

[187]

Real PJ,De Juan A,Lopez-Vega JM.Resistance to chemotherapy via Stat3-dependent overexpression of Bcl-2 in metastatic breast cancer cells.Oncogene2002;21:7611-8

[188]

Barry SP,Knight RA,Latchman DS.STAT3 modulates the DNA damage response pathway.Int J Exp Pathol2010;91:506-14 PMCID:PMC3010549

[189]

Zhang J,Wang JG,Huang GD.Dihydroartemisinin affects STAT3/DDA1 signaling pathway and reverses breast cancer resistance to cisplatin.Am J Chin Med2023;51:445-59

[190]

Chen KF,Liu TH.Sorafenib overcomes TRAIL resistance of hepatocellular carcinoma cells through the inhibition of STAT3.Clin Cancer Res2010;16:5189-99

[191]

Carlisi D,Angileri L.Parthenolide sensitizes hepatocellular carcinoma cells to TRAIL by inducing the expression of death receptors through inhibition of STAT3 activation.J Cell Physiol2011;226:1632-41

[192]

Zeng B,Zheng K.Design, synthesis and in vivo anticancer activity of novel parthenolide and micheliolide derivatives as NF-κB and STAT3 inhibitors.Bioorg Chem2021;111:104973

[193]

Feng J,Bao R.Enantioselective and collective total syntheses of xanthanolides.Angew Chem Int Ed Engl2017;56:16323-7

[194]

Zahra M,George BP.Green nanotech paradigm for enhancing sesquiterpene lactone therapeutics in cancer.Biomed Pharmacother2024;173:116426

[195]

Najafi M,Mortezaee K.Cancer stem cells (CSCs) in cancer progression and therapy.J Cell Physiol2019;234:8381-95

[196]

Nguyen NP,Chi A.Molecular biology of breast cancer stem cells: potential clinical applications.Cancer Treat Rev2010;36:485-91

[197]

Yang YI,Lee KT.Costunolide induces apoptosis in platinum-resistant human ovarian cancer cells by generating reactive oxygen species.Gynecol Oncol2011;123:588-96

[198]

Carlisi D,Di Fiore R.Parthenolide and DMAPT exert cytotoxic effects on breast cancer stem-like cells by inducing oxidative stress, mitochondrial dysfunction and necrosis.Cell Death Dis2016;7:e2194 PMCID:PMC4855673

[199]

Tsuchiya H.Immune evasion by cancer stem cells.Regen Ther2021;17:20-33 PMCID:PMC7966825

[200]

Cai Z,Hu K.Parthenolide enhances the metronomic chemotherapy effect of cyclophosphamide in lung cancer by inhibiting the NF-kB signaling pathway.World J Clin Oncol2024;15:895-907 PMCID:PMC11271733

[201]

Cao D,Xia JN.Artesunate promoted anti-tumor immunity and overcame EGFR-TKI resistance in non-small-cell lung cancer by enhancing oncogenic TAZ degradation.Biomed Pharmacother2022;155:113705

[202]

Wang L,Liu P.Dissection of mechanisms of Chinese medicinal formula Realgar-Indigo naturalis as an effective treatment for promyelocytic leukemia.Proc Natl Acad Sci U S A2008;105:4826-31 PMCID:PMC2290784

[203]

Gong RH,Huang C.Synergisitic anti-colorectal cancer effects of WNT974 combined with artesunate via cooperative regulation of p21, p27, and AKT.Pharmacol Res Mod Chin Med2024;12:100498

[204]

Gong RH,Kwan HY,Chen GQ.Cell death mechanisms induced by synergistic effects of halofuginone and artemisinin in colorectal cancer cells.Int J Med Sci2022;19:175-85 PMCID:PMC8692125

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