Eriocalyxin B inhibits proliferation and induces apoptosis through down-regulation of Bcl-2 and activation of caspase-3 in human bladder cancer cells
Eriocalyxin B (EriB) has been shown to possess promising anticancer potential against various cancer cells. However, its effect against bladder cancer cells remained unexplored. In this study, for the first time, we investigated the effects of EriB on cell proliferation, cell cycle, and apoptosis in bladder cancer T24 cells. In order to examine the effects of EriB on cell proliferation, cell cycle, and apoptosis, we performed MTT assay, flow cytometric analysis and western blot. The results revealed that EriB decreased the cell viability of T24 cells. Flow cytometric analysis demonstrated that EriB markedly induced apoptosis of T24 cells and arrested cell cycle at G2/M phase in a dose-dependent manner. Further characterization showed that EriB involved in the down-regulation of Bcl-2 and activation of caspase-3 before culminating in apoptosis in EriB-treated T24 cells. These in vitro results suggested that EriB should be further examined for in vivo activity in human bladder cancer.
Adams JM. Ways of dying: Multiple pathways to apoptosis. Genes Dev. 2003; 17: 2481-95.
Adams JM, Cory S. The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene 2007; 26: 1324-37.
Amin AR, Kucuk O, Khuri FR, Shin DM. Perspectives for cancer prevention with natural compounds. J Clin Oncol. 2009; 27: 2712-25.
Burlacu A. Regulation of apoptosis by Bcl-2 family proteins. J Cell Mol Med. 2003; 7: 249-57.
Clark PE. Bladder cancer. Curr Opin Oncol. 2007; 19: 241-47.
Cohen GM. Caspases: The executioners of apoptosis. Biochem J. 1997; 326 ( Pt 1): 1-16.
Cragg GM, Newman DJ. Plants as a source of anti-cancer agents. J Ethnopharmacol. 2005; 100: 72-79.
Danial NN. BCL-2 family proteins: critical checkpoints of apoptotic cell death. Clin Cancer Res. 2007; 13: 7254-63.
Elmore S. Apoptosis: A review of programmed cell death. Toxicol Pathol. 2007; 35: 495-516.
Fulda S. Evasion of apoptosis as a cellular stress response in cancer. Int J Cell Biol. 2010; 2010: 370835.
Garcia PA, de Oliveira AB, Batista R. Occurrence, biological activities and synthesis of kaurane diterpenes and their glycosides. Molecules 2007; 12: 455-83.
Grana X, Reddy EP. Cell cycle control in mammalian cells: role of cyclins, cyclin dependent kinases (CDKs), growth suppressor genes and cyclin-dependent kinase inhibitors (CKIs). Oncogene 1995; 11: 211-19.
Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000; 100: 57-70.
Hanson JR. Diterpenoids. Nat Prod Rep. 2004; 21: 785-93.
Hengartner MO. The biochemistry of apoptosis. Nature 2000; 407: 770-76.
Ikezoe T, Chen SS, Tong XJ, Heber D, Taguchi H, Koeffler HP. Oridonin induces growth inhibition and apoptosis of a variety of human cancer cells. Int J Oncol. 2003; 23: 1187-93.
Jeong SY, Seol DW. The role of mitochondria in apoptosis. BMB Rep. 2008; 41: 11-22.
Kanno S, Kitajima Y, Kakuta M, Osanai Y, Kurauchi K, Ujibe M, Ishikawa M. Costunolide-induced apoptosis is caused by receptor-mediated pathway and inhibition of telomerase activity in NALM-6 cells. Biol Pharm Bull. 2008; 31: 1024-28.
Kluck RM, Bossy-Wetzel E, Green DR, Newmeyer DD. The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis. Science 1997; 275: 1132-36.
Lawen A. Apoptosis-an introduction. Bioessays 2003; 25: 888-96.
Lee MG, Lee KT, Chi SG, Park JH. Costunolide induces apoptosis by ROS-mediated mitochondrial permeability transition and cytochrome C release. Biol Pharm Bull. 2001; 24: 303-06.
Leist M, Jaattela M. Four deaths and a funeral: From caspases to alternative mechanisms. Nat Rev Mol Cell Biol. 2001; 2: 589-98.
Leizer AL, Alvero AB, Fu HH, Holmberg JC, Cheng YC, Silasi DA, Rutherford T, Mor G. Regulation of inflammation by the NF-kappaB pathway in ovarian cancer stem cells. Am J Reprod Immunol. 2010; 65: 438-47.
Li L, Yue GG, Lau CB, Sun H, Fung KP, Leung PC, Han Q, Leung PS. Eriocalyxin B induces apoptosis and cell cycle arrest in pancreatic adenocarcinoma cells through caspase- and p53-dependent pathways. Toxicol Appl Pharmacol. 2012; 262: 80-90.
Mallat Z, Tedgui A. Apoptosis in the vasculature: mechanisms and functional importance. Br J Pharmacol. 2000; 130: 947-62.
Park HJ, Kwon SH, Han YN, Choi JW, Miyamoto K, Lee SH, Lee KT. Apoptosis-inducing costunolide and a novel acyclic monoterpene from the stem bark of Magnolia sieboldii. Arch Pharm Res. 2001; 24: 342-48.
Ploeg M, Aben KK, Kiemeney LA. The present and future burden of urinary bladder cancer in the world. World J Urol. 2009; 27: 289-93.
Porter AG, Janicke RU. Emerging roles of caspase-3 in apoptosis. Cell Death Differ. 1999; 6: 99-104.
Rasul A, Bao R, Malhi M, Zhao B, Tsuji I, Li J, Li X. Induction of Apoptosis by Costunolide in Bladder Cancer Cells is Mediated through ROS Generation and Mitochondrial Dysfunction. Molecules 2013; 18: 1418-33.
Rasul A, Ding C, Li X, Khan M, Yi F, Ali M, Ma T. Dracorhodin perchlorate inhibits PI3K/Akt and NF-kappaB activation, up-regulates the expression of p53, and enhances apoptosis. Apoptosis 2012a; 17: 1104-19.
Rasul A, Khan M, Yu B, Ma T, Yang H. Xanthoxyletin, a coumarin induces S phase arrest and apoptosis in human gastric adenocarcinoma SGC-7901 cells. Asian Pac J Cancer Prev. 2011a; 12: 1219-23.
Rasul A, Song R, Wei W, Nishino Y, Tsuji I, Li X, Li J. Tubeimoside-1 inhibits growth via the induction of cell cycle arrest and apoptosis in human melanoma A375 cells. Bangladesh J Pharmacol. 2012b; 7: 150-56.
Rasul A, Yu B, Khan M, Zhang K, Iqbal F, Ma T, Yang H. Magnolol, a natural compound, induces apoptosis of SGC-7901 human gastric adenocarcinoma cells via the mitochondrial and PI3K/Akt signaling pathways. Int J Oncol. 2012c; 40: 1153-61.
Rasul A, Yu B, Yang LF, Ali M, Khan M, Ma T, Yang H. Induction of mitochondria-mediated apoptosis in human gastric adenocarcinoma SGC-7901 cells by kuraridin and Norkurarinone isolated from Sophora flavescens. Asian Pac J Cancer Prev. 2011b; 12: 2499-2504.
Rasul A, Yu B, Zhong L, Khan M, Yang H, Ma T. Cytotoxic effect of evodiamine in SGC-7901 human gastric adenocarcinoma cells via simultaneous induction of apoptosis and autophagy. Oncol Rep. 2012d; 27: 1481-87.
Reed JC. Bcl-2 family proteins. Oncogene 1998; 17: 3225-36.
Reed JC. Dysregulation of apoptosis in cancer. J Clin Oncol. 1999; 17: 2941-53.
Reed JC. Apoptosis-based therapies. Nat Rev Drug Discov. 2002; 1: 111-21.
Ricci MS, Zong WX. Chemotherapeutic approaches for targeting cell death pathways. Oncologist 2006; 11: 342-57.
Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012; 62: 10-29.
Srivastava JK, Gupta S. Tocotrienol-rich fraction of palm oil induces cell cycle arrest and apoptosis selectively in human prostate cancer cells. Biochem Biophys Res Commun. 2006; 346: 447-53.
Vermeulen K, Van Bockstaele DR, Berneman ZN. The cell cycle: A review of regulation, deregulation and therapeutic targets in cancer. Cell Prolif. 2003; 36: 131-49.
Wang L, Zhao WL, Yan JS, Liu P, Sun HP, Zhou GB, Weng ZY, Wu WL, Weng XQ, Sun XJ, Chen Z, Sun HD, Chen SJ. Eriocalyxin B induces apoptosis of t(8;21) leukemia cells through NF-kappaB and MAPK signaling pathways and triggers degradation of AML1-ETO oncoprotein in a caspase-3-dependent manner. Cell Death Differ. 2007; 14: 306-17.
Wang X. The expanding role of mitochondria in apoptosis. Genes Dev. 2001; 15: 2922-33.
Xu Y, Chiu JF, He QY, Chen F. Tubeimoside-1 exerts cytotoxicity in HeLa cells through mitochondrial dysfunction and endoplasmic reticulum stress pathways. J Proteome Res. 2009; 8: 1585-93.
Zhang YW, Jiang XX, Chen QS, Shi WY, Wang L, Sun HD, Shen ZX, Chen Z, Chen SJ, Zhao WL. Eriocalyxin B induces apoptosis in lymphoma cells through multiple cellular signaling pathways. Exp Hematol. 2010; 38: 191-201.
Copyright (c) 2013 Azhar Rasul, Jinmei Liu, Ying Liu, Faya Martin Millimouno, Xiaowan Wang, Ichiro Tsuji, Takaki Yamamura, Jiang Li, Xiaomeng Li
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).