Cytotoxicity of paeonenoide C isolated from Paeonia obovata on HT-29 human colon cancer cells
DOI:
https://doi.org/10.3329/bjp.v20i1.78798Keywords:
Colon cancer, Cytotoxicity, ERK1/2, HT-29 cell line, Paeonenoide C , Paeonia obovata, RetinoblastomaAbstract
In this study, an alternative approach to activity-based screening was employed to identify potential anti-cancer agent against colon cancer. As a result, Paeonia obovata was selected, and an active compound was isolated from its methanol extracts. Through structural and physicochemical analyses, the compound was identified as paeonenoide C, a triterpenoid. Various cell-based assays, including the MTT reduction assay, LDH release assay, and colony formation assay were conducted to assess its anti-cancer properties. Paeonenoide C exhibited cytotoxic effects in HT-29 human colon cancer cells at concentrations above 150 μM. Western blot analysis demonstrated that paeonenoide C-induced cell cycle arrest and apoptosis by suppressing the phosphorylation of retinoblastoma protein and extracellular signal-regulated kinases 1/2 while down-regulating extracellular signal-regulated kinases 1/2 expression. These findings suggest that paeonenoide C possesses potential anti-cancer activity against colon cancer cell lines.
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Brown JM, Giaccia AJ. The unique physiology of solid tumors: Opportunities (and problems) for cancer therapy. Cancer Res. 1998; 58: 1408-16.
Brown MD, Sacks DB. Protein scaffolds in MAP kinase signaling. Cell Signal. 2009; 21: 462-69.
Chang X, Wang S, Bao YR, Li TJ, Yu XM, Meng XS. Multicomponent, multitarget integrated adjustment: Metabolomics study of qizhiweitong particles curing gastrointestinal motility disorders in mice induced by atropine. J Ethnopharmacol. 2016; 189: 14-21.
Chattopadhyay S, Bisaria VS, Panda AK, Srivastava AK. Cytotoxicity of in vitro produced podophyllotoxin from Podophyllum hexandrum on human cancer cell line. Nat Prod Res. 2004; 18: 51-57.
da Rocha AB, Lopes RM, Schwartsmann G. Natural products in anti-cancer therapy. Curr Opin Pharmacol. 2001; 1: 364-69.
Decker T, Lohmann-Matthes ML. A quick and simple method for the quantitation of lactate dehydrogenase release in measurements of cellular cytotoxicity and tumor necrosis factor (TNF) activity. J Immunol Methods. 1988; 115: 61-69.
de Gramont A, Figer A, Seymour M, Homerin M, Hmissi A, Cassidy J, Boni C, Cortes-Funes H, Cervantes A, Freyer G, Papamichael D, Le Bail N, Louvet C, Hendlern C, Morvan F, Bonetti A. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol. 2000; 18: 2938-47.
Fan Z, Liu J, Wang X, Yang S, Wang Q, Yan L, Zhang Y, Wu X. Paeoniae radix Rubra: A review of ethnopharmacology, phytochemistry, pharmacological activities, therapeutic mechanism for blood stasis syndrome, and quality control. Chem Biodivers. 2024; 21: e202401119.
Fisher B. Clinical trials for the evaluation of cancer therapy. Cancer 1984; 54: 2609-17.
Gouaze V, Yu JY, Bleicher RJ, Han TY, Liu YY, Wang H, Gottesman MM, Bitterman A, Giuliano AE, Cabot MC. Overexpression of glucosylceramide synthase and P-glycoprotein in cancer cells selected for resistance to natural product chemotherapy. Mol. Cancer Ther. 2004; 3: 633-39.
Halina E, Marta K, Agnieszka S. Paeonia × suffruticosa (Moutan Peony): A review of the chemical composition, traditional and professional use in medicine, position in cosmetics industries, and biotechnological studies. Plants 2002; 11: 3379.
Jedinak A, Sliva D. Pleurotus ostreatus inhibits proliferation of human breast and colon cancer cells through p53-dependent as well as p53-independent pathway. Int J Oncol. 2008; 33: 1307-13.
Jemal A, Siegel R, Xu J, Ward E. Cancer statistics. CA Cancer J Clin. 2010; 60: 277-300.
Kamb A. Cell-cycle regulators and cancer. Trends Genet. 1995; 11: 136-40.
Kerr JF, Winterford CM, Harmon BV. Apoptosis: Its significance in cancer and cancer therapy. Cancer 1994; 73: 2013-26.
Kinghorn AD, Chin YW, Swanson SM. Discovery of natural product anti-cancer agents from biodiverse organisms. Curr Opin Drug Discov Devel. 2009; 12: 189-96.
Knudsen ES, Knudsen KE. Retinoblastoma tumor suppressor: Where cancer meets the cell cycle. Exp Biol Med. 2006; 231: 1271-81.
Kodach LL, Bos CL, Duran N, Peppelenbosch MP, Ferreira CV, Hardwick JCH. Violacein synergistically increases 5-fluorouracil cytotoxicity, induces apoptosis and inhibits Akt-mediated signal transduction in human colorectal cancer cells. Carcinogenesis 2006; 27: 508-16
Koo YK, Kim JM , Koo JY, Kang SS, Bae KH, Kim YS, Chung JH, Yun-Choi HS. Platelet anti-aggregatory and blood anti-coagulant effects of compounds isolated from Paeonia lactiflora and Paeonia suffruticosa. Pharmazie 2010; 65: 624-28.
Kozlenko M, Vol A, Zusman I. Stability-variability conflict as a reason for cancer: Physical and social aspects. Med Hypotheses. 2001; 57: 648-54.
Kwon HJ, Hong YK, Park C, Choi YH, Yun HJ, Lee EW, Kim BW. Widdrol induces cell cycle arrest, associated with MCM down-regulation, in human colon adenocarcinoma cells. Cancer Lett. 2010; 290: 96-103.
Lee KH. Discovery and development of natural product-derived chemotherapeutic agents based on a medicinal chemistry approach. J Nat Prod. 2010; 73: 500-16.
Lim do Y, Jeong Y, Tyner AL, Park JH. Induction of cell cycle arrest and apoptosis in HT-29 human colon cancer cells by the dietary compound luteolin. Am J Physiol Gastrointest Liver Physiol. 2007; 292: G66-75.
Maroun JA, Anthony LB, Blais N, Burkes R, Dowden SD, Dranitsaris G, Samson B, Shah A, Thirlwell MP, Vincent MD, Wong R. Prevention and management of chemotherapy-induced diarrhea in patients with colorectal cancer: A consensus statement by the Canadian working group on chemotherapy-induced diarrhea. Curr Oncol. 2007; 14: 13-20.
Ogiso Y, Tomida A, Lei S, Omura S, Tsuruo T. Proteasome inhibition circumvents solid tumor resistance to topoisomerase ІІ-directed drugs. Cancer Res. 2000; 60: 2429-34.
Park HR, Tomida A, Sato S, Tsukumo Y, Yun J, Yamori T, Hayakawa Y, Tsuruo T, Shinya K: Effect on tumor cells of blocking survival response to glucose deprivation. J Natl Can Inst 2004; 96: 1300-10.
Pozzi A, Yan X, Macias-Perez I, Wei S, Hata AN, Breyer RM, Morrow JD, Capdevila JH. Colon carcinoma cell growth is associated with prostaglandin E2/EP4 receptor-evoked ERK activation. J Biol Chem. 2004; 279: 29797-804.
Roskoski R Jr. ERK1/2 MAP kinases: Structure, function, and regulation. Pharmacol Res. 2012; 66: 105-43.
Sun Y, Sinicrope FA. Selective inhibitors of MEK1/ERK44/42 and p38 mitogen-activated protein kinases potentiate apoptosis induction by sulindac sulfide in human colon carcinoma cells. Mol Cancer Ther. 2005; 4: 51-59.
Tomida A, Tsuruo T. Drug resistance mediated by cellular stress response to the microenvironment of solid tumors. Anticancer Drug Des. 1999; 14: 169-77.
Tsuruo T, Naito M, Tomida A, Fujita N, Mashima T, Sakamoto H, Haga N. Molecular targeting therapy of cancer: Drug resistance, apoptosis and survival signal. Cancer Sci. 2003; 93: 15-21.
Weinberg RA. The retinoblastoma protein and cell cycle control. Cell 1995; 81: 323-30.
Wu L, Nie L, Wang Q, Xu Z, Wang Y, He C, Song J, Yao H. Comparative and phylogenetic analyses of the chloroplast genomes of species of Paeoniaceae. Sci Rep. 2021; 11: 14643.
Wu, S.H., Yang, S.M., Wu, D.G., Cheng, Y.W., Peng, Q. 2005. Three novel 24,30-dinortriterpenoids, paeonenoides A-C, from Paeonia veitchii. Helv. Chim. Acta. 2005; 88: 259-65.
Yang SA, Paek SH, Kozukue N, Lee KR, Kim JA. Alpha-chaconine, a potato glycoalkaloid, induces apoptosis of HT-29 human colon cancer cells through caspase-3 activation and inhibition of ERK1/2 phosphorylation. Food Chem Toxicol. 2006; 44: 839-46.
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