Triptolide inhibits cell growth and induces G0- G1 arrest by regulating P21wap1/cip1 and P27 kip1 in human multiple myeloma RPMI-8226 cells
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
To investigate the effects of triptolide(TPL) on cell growth, cell cycle and the expressions of p21wap1/cip1 and p27kip1.
MTT assay was used to determine the cell viability after triptolide treatment in human multiple myeloma RPMI-8226 cells. The effect on cell cycle distribution was determined by flow cytometry. Semi-quantitative reverse transcription-PCR was used to examine the mRNA expressions of p21wap1/cip1 and p27kip1. The protein expressions of p21 wap1/cip1 and p27kip1 were determined by Western blot.
Triptolide of varying concentrations induced cell viability inhibition in dose- and time-related fashion and caused G0-G1 phase arrest of cell cycle progression in RPMI-8226 cells. These effects accompanied with up-modulation of the expressions of p21 wap1/cip1 and p27kip1.
These results suggest that triptolide inhibit cell proliferation and cell cycle progression via up-regulating p21wap1/cip1 and p27kip1 and triptolide may exert its anti-cancer activity through this pathway.
- Lou YJ, Jin J. Triptolide down-regulates bcr-abl expression and induces apoptosis in chronic myelogennous leukemia cells[J]. Leuk Lymphoma 2004; 45: 373–376. CrossRef
- Tang XY, Zhu YQ, Tao WH, et al. Synergistic effect of triptolide combined with 5-fluorouracil on colon carcinoma[J]. Postgrad Med J 2007; 83: 338–343. CrossRef
- Jan HJ, Lee CC, Lin YM, et al. Rosiglitazone reduces cell invasiveness by inducing MKP-1 in human U87MG glioma cells[J]. Cancer Lett 2009; 277: 141–148. CrossRef
- Liang M, Fu J. Triptolide inhibits interferon-gammainduced programmed death-1-ligand 1 surface expression in breast cancer cell[J]. Cancer Lett 2008; 270: 337–341. CrossRef
- Philips PA, Dudeja V, McCarroll JA, et al. Triptolide induces pancreatic cancer cell death via inhibition of heat shock protein 70[J]. Cancer Res 2007; 67: 9407–9416. CrossRef
- Roy S, Gu M, Ramasamy K, et al. p21/Cip1 and p27/Kip1 are essential molecular targets of inositol hexahosphate for its antitumor efficacy against prostate cancer[J]. Cancer Res 2009; 69: 1166–1173. CrossRef
- Baiz D, Pozzato G, Dapas B, et al. Bortezomib arrests the proliferation of hepatocellular carcinoma cells HepG2 and JHH6 by differentially affecting E2F1, p21 and p27 levels[J]. Biochimie 2009; 91: 373–382. CrossRef
- Besson A, Dowdy SF, Roberts JM. CDK inhibitors: cell cycle regulators and beyond[J]. Dev Cell 2008; 14: 159–169. CrossRef
- Gao F, Yi J, Yuan JQ, et al. The cell cycle related apoptotic susceptibility to arsenic trioxide is associated with the level of reactive oxygen species[J]. Cell Res 2004; 14: 81–85. CrossRef
- Carter BZ, Mak DH, Schober WD, et al. Triptolide induces caspase-dependent cell death mediated via the mitochondrial pathway in leukemia cells[J]. Blood 2006; 108: 630–637. CrossRef
- Krug U, Ganser A, Koeffler HP. Tumor suppressor genes in normal and malignant hematopoiesis[J]. Oncogene 2002; 21: 3475–3495 CrossRef
- Zanetti M, Stocca A, Dapas B, et al. Inhibitory effects of fenofibrate on apoptosis and cell proliferation in human endothelial cells in high glucose[J]. J Mol Med 2008; 86: 185–195. CrossRef
- Singh RP, Agarwal R. Natural flavonoids targeting deregulated cell cycle progression in cancer cells[J]. Curr Drug Targets 2006; 7: 345–354. CrossRef
- Athar M, Back JH, Kopelovich L, et al. Multiple, molecular targets of resveratrol: anti-carcinogenic mechanisms[J]. Arch Biochem Biophys 2009; 486: 95–102. CrossRef
- Coqueret O. New roles for p21 and p27 cell-cycle inhibitors: a function for each cell compartment[J]? Trends Cell Biol 2003; 13: 65–70. CrossRef
- Tian Y, Song Y. Effects of inositol hexaphosphate on proliferation of HT-29 human colon carcinoma cell line[J]. World J Gastroenterol 2006; 12: 4137–4142.
- Roy S, Singh RP, Aqarwal C, et al. Downregulation of both p21/Cip1 and p27/kip1 produces a more aggressive prostate cancer phenotype[J]. Cell Cycle 2008; 7: 1828–1835.
- Enders GH, Maude SL. Traffic safety for the cell: influence of cyclin-dependent kinase activity on genomic stability[J]. Gene 2006; 371: 1–6. CrossRef
- Schwartz GK, Shah MA. Targeting the cell cycle: a new approach to cancer therapy[J]. J Clin Oncol 2005; 23: 9408–9421. CrossRef
- Zheng JY, Wang WZ, Li KZ, et al. Effect of p27(kip1) on cell cycle and apoptosis in gastric cancer cells[J]. World J Gastroenterol 2005; 11: 7072–7077.
- Laochim E, Michael M, Stavropoulos NE, et al. Expression patterns of cyclinD1, E and cyclindependent kinase inhibitors p21wap1/Cip1 and p27/Kip1 in Urothelial carcinoma: Correlation with other cell-cycle-related proteins (Rb, p53, Ki-67 and PCNA) and clinicopathological features[J]. Urol Int 2004; 73: 65–73. CrossRef
- Korkolopoulou P, Christodoulou P, Konstantinidou AE, et al. Cell cycle regulators in bladder cancer: A multivariate survival study with emphasis on p27kip1[J]. Hum Pathol 2000; 31: 751–760. CrossRef
- Katner AL, Hoang QB, Gootam P, et al. Induction of cell cycle arrest and apoptosis in human prostate carcinoma cells by a recombinant adenovirus expressing P27kip1[J]. Prostate 2002; 53: 77–87. CrossRef
- Onumah OE, Jules GE, Zhao Y, et al. Overexpression of catalase delays G0- G1 to S phase transition during cell cycle progression in mouse aortic endothelial cells[J]. Free Radic Biol Med 2009; 46: 1658–1667. CrossRef
- Roy S, Kaur M, Aqarwal C, et al. p21 and p27 induction by silibinin is essential for its cellcycle arrest effect in prostate carcinoma cells[J]. Mol Cancer Ther 2007; 6: 2696–2707. CrossRef
- Triptolide inhibits cell growth and induces G0- G1 arrest by regulating P21wap1/cip1 and P27 kip1 in human multiple myeloma RPMI-8226 cells
Chinese Journal of Cancer Research
Volume 22, Issue 2 , pp 141-147
- Cover Date
- Print ISSN
- Online ISSN
- Chinese Anti-Cancer Association
- Additional Links
- RPMI-8226 cells
- Cell cycle
- Multiple myeloma