title: Tetrandrine triggers apoptosis and cell cycle arrest in human renal cell carcinoma cells.
abstract: Tetrandrine is a cytotoxic compound capable of exerting remarkable antitumor activity against many cancer cells in vitro and in vivo. However, little is known about its effect on human renal cell carcinoma (RCC). In the present study, using RCC 786-O, 769-P and ACHN cell lines as the model system, we demonstrated the anticancer effect of tetrandrine against RCC and clarified its underlying mechanisms. Tetrandrine treatment showed growth inhibitory effects on RCC cells in a time- and dose-dependent manner. Additionally, flow cytometric studies revealed that tetrandrine was capable of inducing G1 cell cycle arrest and apoptosis in RCC cells. Mechanically, activation of caspase-8, caspase-9, and caspase-3 and increasing expression of cell cycle regulatory protein p21(WAF1/CIP1) and p27(KIP1) were observed in tetrandrine-treated RCC cells. This study provides the first evidence that tetrandrine triggered apoptosis and cell cycle arrest in RCC 786-O, 769-P and ACHN cells in vitro; these events are associated with caspase cascade activation and upregulation of p21 and p27. Our results thus provide rational evidence supporting the application of tetrandrine as a novel therapeutic agent against RCC in the clinical setting.
authors.affiliation: Department of Urology, The Affiliated Hospital of Medical College Qingdao University, Qingdao, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.forename: Bing
authors.initials: B
authors.lastname: Ji
authors.forename: Yancui
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D044182:Benzylisoquinolines / Q000494:pharmacology*; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000473:pathology*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D044182:Benzylisoquinolines; C493956:CDKN1A protein, human; C436291:CDKN1B protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; C009438:tetrandrine; D020169:Caspases
references.citation: Exp Biol Med (Maywood). 2006 Feb;231(2):117-29
references.pmid: 16446487
references.citation: Nat Rev Cancer. 2009 Mar;9(3):153-66
references.pmid: 19238148
references.citation: Int J Cancer. 2011 Sep 15;129(6):1519-31
references.pmid: 21128229
references.citation: Oncol Rep. 2012 Nov;28(5):1681-6
references.pmid: 22941407
references.citation: Mol Pharm. 2012 Feb 6;9(2):222-9
references.pmid: 22171565
references.citation: Mol Cancer Ther. 2011 Jan;10(1):104-16
references.pmid: 21220495
references.citation: N Engl J Med. 2007 Jan 11;356(2):115-24
references.pmid: 17215529
references.citation: Dev Growth Differ. 2011 Feb;53(2):137-48
references.pmid: 21338340
references.citation: Diabetes. 1992 May;41(5):616-9
references.pmid: 1568531
references.citation: J Surg Res. 2011 Mar;166(1):e45-51
references.pmid: 21176918
references.citation: Cancer Res. 2004 Dec 15;64(24):9086-92
references.pmid: 15604277
references.citation: Cancer Biol Ther. 2008 Jul;7(7):1073-8
references.pmid: 18437054
references.citation: Int J Toxicol. 2011 Feb;30(1):35-46
references.pmid: 21224419
references.citation: J Natl Cancer Inst. 2012 Jan 18;104(2):93-113
references.pmid: 22235142
references.citation: Anticancer Drugs. 1998 Jan;9(1):77-81
references.pmid: 9491795
references.citation: J Clin Oncol. 1999 Aug;17(8):2530-40
references.pmid: 10561319
references.citation: Cancer Lett. 2010 Jan 28;287(2):187-95
references.pmid: 19586712
references.citation: Anticancer Agents Med Chem. 2010 Sep;10(7):534-42
references.pmid: 20879981
references.citation: Int J Cancer. 2009 May 15;124(10):2260-9
references.pmid: 19165864
references.citation: J Ethnopharmacol. 2002 Jul;81(2):225-9
references.pmid: 12065155
references.citation: Expert Rev Mol Med. 2008 Jul 01;10:e19
references.pmid: 18590585
references.citation: Acta Pharmacol Sin. 2002 Dec;23(12):1102-6
references.pmid: 12466047
references.citation: Front Biosci. 2008 Jan 01;13:2191-202
references.pmid: 17981702
references.citation: Mol Pharmacol. 2011 Feb;79(2):211-9
references.pmid: 20978119
references.citation: Eur Urol. 2011 Oct;60(4):615-21
references.pmid: 21741761
references.citation: J Vet Sci. 2009 Mar;10(1):23-8
references.pmid: 19255520
references.citation: N Engl J Med. 2007 Jan 11;356(2):125-34
references.pmid: 17215530