Root Extract of Trichosanthes kirilowii Suppresses Metastatic Activity of EGFR TKI-Resistant Human Lung Cancer Cells by Inhibiting Src-Mediated EMT

References

• Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;73(1):17–48. doi: 10.3322/caac.21763
   PubMed Web of Science ®Google Scholar
• Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, Felip E, Broderick SR, Brahmer JR, Swanson SJ, et al. Neoadjuvant nivolumab plus chemotherapy in resectable lung cancer. N Engl J Med. 2022;386(21):1973–1985. doi: 10.1056/NEJMoa2202170
   PubMed Web of Science ®Google Scholar
• Passaro A, Jänne PA, Mok T, Peters S. Overcoming therapy resistance in EGFR-mutant lung cancer. Nat Cancer. 2021;2(4):377–391. doi: 10.1038/s43018-021-00195-8
   PubMedGoogle Scholar
• Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, Harris PL, Haserlat SM, Supko JG, Haluska FG, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004;350(21):2129–2139. doi: 10.1056/NEJMoa040938
   PubMed Web of Science ®Google Scholar
• Paez JG, Jänne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman P, Kaye FJ, Lindeman N, Boggon TJ, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004;304(5676):1497–1500. doi: 10.1126/science.1099314
   PubMed Web of Science ®Google Scholar
• Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361(10):947–957. doi: 10.1056/NEJMoa0810699
   PubMed Web of Science ®Google Scholar
• Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012;13(3):239–246. doi: 10.1016/S1470-2045(11)70393-X
   PubMed Web of Science ®Google Scholar
• Sequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai CM, Boyer M, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2023;41(16):2869–2876. doi: 10.1200/JCO.2012.44.2806
   PubMed Web of Science ®Google Scholar
• Ramalingam SS, Vansteenkiste J, Planchard D, Cho BC, Gray JE, Ohe Y, Zhou C, Reungwetwattana T, Cheng Y, Chewaskulyong B, et al. Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC. N Engl J Med. 2020;382(1):41–50. doi: 10.1056/NEJMoa1913662
   PubMed Web of Science ®Google Scholar
• Yun CH, Mengwasser KE, Toms AV, Woo MS, Greulich H, Wong KK, Meyerson M, Eck MJ. The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP. Proc Natl Acad Sci USA. 2008;105(6):2070–2075. doi: 10.1073/pnas.0709662105
   PubMed Web of Science ®Google Scholar
• Zhu X, Chen L, Liu L, Niu X. EMT-mediated acquired EGFR-TKI resistance in NSCLC: mechanisms and strategies. Front Oncol. 2019;9:1044. doi: 10.3389/fonc.2019.01044
   PubMed Web of Science ®Google Scholar
• Shibue T, Weinberg RA. EMT, CSCs, and drug resistance: the mechanistic link and clinical implications. Nat Rev Clin Oncol. 2017;14(10):611–629. doi: 10.1038/nrclinonc.2017.44
   PubMed Web of Science ®Google Scholar
• Ye X, Weinberg RA. Epithelial-mesenchymal plasticity: a central regulator of cancer progression. Trends Cell Biol. 2015;25(11):675–686. doi: 10.1016/j.tcb.2015.07.012
   PubMed Web of Science ®Google Scholar
• Chung JH, Rho JK, Xu X, Lee JS, Yoon HI, Lee CT, Choi YJ, Kim HR, Kim CH, Lee JC. Clinical and molecular evidences of epithelial to mesenchymal transition in acquired resistance to EGFR-TKIs. Lung Cancer. 2011;73(2):176–182. doi: 10.1016/j.lungcan.2010.11.011
   PubMed Web of Science ®Google Scholar
• Lee AF, Chen MC, Chen CJ, Yang CJ, Huang MS, Liu YP. Reverse epithelial-mesenchymal transition contributes to the regain of drug sensitivity in tyrosne kinase inhibitor-resistant non-small cell lung cancer cells. PLOS One. 2017;12(7):e0180383. doi: 10.1371/journal.pone.0180383
   PubMed Web of Science ®Google Scholar
• Minh CV, Nhiem NX, Yen HT, Kiem PV, Tai BH, Le Tuan Anh H, Hien TT, Park S, Kim N, Kim SH. Chemical constituents of Trichosanthes kirilowii and their cytotoxic activities. Arch Pharm Res. 2015;38(8):1443–1448. doi: 10.1007/s12272-014-0490-6
   PubMed Web of Science ®Google Scholar
• Kim SR, Seo HS, Choi HS, Cho SG, Kim YK, Hong EH, Shin YC, Ko SG. Trichosanthes kirilowii ethanol extract and cucurbitacin D inhibit cell growth and induce apoptosis through inhibition of STAT3 activity in breast cancer cells. Evid Based Complement Alternat Med. 2013;2013:975350. doi: 10.1155/2013/975350
   PubMed Web of Science ®Google Scholar
• Ryu SY, Lee SH, Choi SU, Lee CO, No Z, Ahn JW. Antitumor activity of Trichosanthes kirilowii. Arch Pharm Res. 1994;17(5):348–353. doi: 10.1007/BF02974175
   Google Scholar
• Akihisa T, Kokke WCMC, Krause JA, Eggleston DS, Katayama SI, Kimura Y, Tamura T. 5-Dehydrokarounidiol [D:c-Friedo-oleana-5,7,9(11)-triene-3a,29-diol], a novel triterpene from Trichosanthes kirilowii MAXIM. Chem Pharm Bull. 1992;40(12):3280–3283. doi: 10.1248/cpb.40.3280
   Web of Science ®Google Scholar
• Jang KC, Lee JH, Kim SC, Song EY, Ro NY, Moon DY, Um YC, Park KH. Antibacterial and radical scavenging activities of 1-C-(p-hydroxyphenyl)-glycerol from Trichosanthes kirilowii. J Appl Biol Chem. 2007;50:17–21.
   Google Scholar
• Zhao J, Ben LH, Wu YL, Hu W, Ling K, Xin SM, Nie HL, Ma L, Pei G. Anti-HIV agent trichosanthin enhances the capabilities of chemokines to stimulate chemotaxis and G protein activation, and this is mediated through interaction of trichosanthin and chemokine receptors. J Exp Med. 1999;190(1):101–111. doi: 10.1084/jem.190.1.101
   PubMed Web of Science ®Google Scholar
• Ku JM, Hong SH, Kim HI, Kim MJ, Kim S-K, Kim M, Choi SY, Park J, Kim HK, Kim JH, et al. Synergistic anticancer effect of combined use of Trichosanthes kirilowii with cisplatin and pemetrexed enhances apoptosis of H1299 non-small-cell lung cancer cells via modulation of ErbB3. Phytomedicine. 2020;66:153109. doi: 10.1016/j.phymed.2019.153109
   PubMed Web of Science ®Google Scholar
• Park HJ, Park SH. The ethanolic extract of Trichosanthes kirilowii root exerts anti-cancer effects in human non-small cell lung cancer cells resistant to EGFR TKI. Nutr Cancer. 2023;75(1):376–387. doi: 10.1080/01635581.2022.2114509
   PubMed Web of Science ®Google Scholar
• Jayaprakasam B, Seeram NP, Nair MG. Anticancer and antiinflammatory activities of cucurbitacins from Cucurbita andreana. Cancer Lett. 2003;189(1):11–16. doi: 10.1016/s0304-3835(02)00497-4
   PubMed Web of Science ®Google Scholar
• Johnson FM, Saigal B, Talpaz M, Donato NJ. Dasatinib (BMS-354825) tyrosine kinase inhibitor suppresses invasion and induces cell cycle arrest and apoptosis of head and neck squamous cell carcinoma and non-small cell lung cancer cells. Clin Cancer Res. 2005;11(19 Pt 1):6924–6932. doi: 10.1158/1078-0432.CCR-05-0757
   PubMed Web of Science ®Google Scholar
• Min TR, Park HJ, Ha KT, Chi GY, Choi YH, Park SH. Suppression of EGFR/STAT3 activity by lupeol contributes to the induction of the apoptosis of human non-small cell lung cancer cells. Int J Oncol. 2019;55(1):320–330. doi: 10.3892/ijo.2019.4799
   PubMed Web of Science ®Google Scholar
• Park HJ, Park SH, Choi YH, Chi GY. The root extract of Scutellaria baicalensis induces apoptosis in EGFR TKI-resistant human lung cancer cells by inactivation of STAT3. Int J Mol Sci. 2021;22(10):5181. doi: 10.3390/ijms22105181
   PubMed Web of Science ®Google Scholar
• Zhang S, Yu D. Targeting Src family kinases in anti-cancer therapies: turning promise into triumph. Trends Pharmacol Sci. 2012;33(3):122–128. doi: 10.1016/j.tips.2011.11.002
   PubMed Web of Science ®Google Scholar
• Liu X, Feng R. Inhibition of epithelial to mesenchymal transition in metastatic breast carcinoma cells by c-Src suppression. Acta Biochim Biophys Sin. 2010;42(7):496–501. doi: 10.1093/abbs/gmq043
   Google Scholar
• Lang L, Shay C, Xiong Y, Thakkar P, Chemmalakuzhy R, Wang X, Teng Y. Combating head and neck cancer metastases by targeting Src using multifunctional nanoparticle-based saracatinib. J Hematol Oncol. 2018;11(1):85. doi: 10.1186/s13045-018-0623-3
   PubMedGoogle Scholar
• Srivastava K, Pickard A, Craig SG, Quinn GP, Lambe SM, James JA, McDade SS, McCance DJ. ΔNp63γ/SRC/slug signaling axis promotes epithelial-to-mesenchymal transition in squamous cancers. Clin Cancer Res. 2018;24(16):3917–3927. doi: 10.1158/1078-0432.CCR-17-3775
   PubMed Web of Science ®Google Scholar
• Kaewmeesri P, Pocasap P, Kukongviriyapan V, Prawan A, Kongpetch S, Senggunprai L. Anti-metastatic potential of natural triterpenoid cucurbitacin B against cholangiocarcinoma cells by targeting Src protein. Integr Cancer Ther. 2022;21:15347354221124861. doi: 10.1177/15347354221124861
   Web of Science ®Google Scholar
• Yuan R, Fan Q, Liang X, Han S, He J, Wang QQ, Gao H, Feng Y, Yang S. Cucurbitacin B inhibits TGF-β1-induced epithelial-mesenchymal transition (EMT) in NSCLC through regulating ROS and PI3K/Akt/mTOR pathways. Chin Med. 2022;17(1):24. doi: 10.1186/s13020-022-00581-z
   PubMed Web of Science ®Google Scholar
• Li CT, Lin CH, Kao TY, Wu MF, Yeh CS, Yeh KT, Ko JL. The mechanisms of action of Tianhua(™) on antitumor activity in lung cancer cells. Pharm Biol. 2010;48(11):1302–1309. doi: 10.3109/13880201003789432
   PubMed Web of Science ®Google Scholar
• Hata A, Katakami N, Yoshioka H, Takeshita J, Tanaka K, Masago K, Fujita S, Kaji R, Imai Y, Monden K, et al. Prognostic impact of central nervous system metastases after acquired resistance to EGFR-TKI: poorer prognosis associated with T790M-negative status and leptomeningeal metastases. Anticancer Res. 2015;35(2):1025–1031.
   PubMed Web of Science ®Google Scholar
• Lam TC, Tsang KC, Choi HC, Lee VH, Lam KO, Chiang CL, So TH, Chan WW, Nyaw SF, Lim F, et al. Combination atezolizumab, bevacizumab, pemetrexed and carboplatin for metastatic EGFR mutated NSCLC after TKI failure. Lung Cancer. 2021;159:18–26. doi: 10.1016/j.lungcan.2021.07.004
   PubMed Web of Science ®Google Scholar
• Saitoh M. Involvement of partial EMT in cancer progression. J Biochem. 2018;164(4):257–264. doi: 10.1093/jb/mvy047
   PubMed Web of Science ®Google Scholar
• Li D, Zhang L, Zhou J, Chen H. Cigarette smoke extract exposure induces EGFR-TKI resistance in EGFR-mutated NSCLC via mediating Src activation and EMT. Lung Cancer. 2016;93:35–42. doi: 10.1016/j.lungcan.2015.12.007
   PubMed Web of Science ®Google Scholar
• Weng CH, Chen LY, Lin YC, Shih JY, Lin YC, Tseng RY, Chiu AC, Yeh YH, Liu C, Lin YT, et al. Epithelial-mesenchymal transition (EMT) beyond EGFR mutations per se is a common mechanism for acquired resistance to EGFR TKI. Oncogene. 2019;38(4):455–468. doi: 10.1038/s41388-018-0454-2
   PubMed Web of Science ®Google Scholar
• Park KS, Raffeld M, Moon YW, Xi L, Bianco C, Pham T, Lee LC, Mitsudomi T, Yatabe Y, Okamoto I, et al. CRIPTO1 expression in EGFR-mutant NSCLC elicits intrinsic EGFR-inhibitor resistance. J Clin Invest. 2014;124(7):3003–3015. doi: 10.1172/JCI73048
   PubMed Web of Science ®Google Scholar
• Choi YK, Cho SG, Woo SM, Yun YJ, Park S, Shin YC, Ko SG. Herbal extract SH003 suppresses tumor growth and metastasis of MDA-MB-231 breast cancer cells by inhibiting STAT3-IL-6 signaling. Mediators Inflamm. 2014;2014:492173. doi: 10.1155/2014/492173
   PubMed Web of Science ®Google Scholar
• Zhang H, Zhao B, Wei H, Zeng H, Sheng D, Zhang Y. Cucurbitacin B controls M2 macrophage polarization to suppresses metastasis via targeting JAK-2/STAT3 signalling pathway in colorectal cancer. J Ethnopharmacol. 2022;287:114915. doi: 10.1016/j.jep.2021.114915
   PubMed Web of Science ®Google Scholar