Inhibition of phospholipase C gamma1 signaling pathway promotes apoptosis of human

Abstract

Abstract: Objective To investigate the effects of inhibiting phospholipase C gamma1 signaling pathway on the apoptosis of human colorectal carcinoma cells. Methods SW620 cells were treated with U73122 in vitro to inhibit the phospholipase C gamma1 signalling pathway and examined under light microscope and transmission electron microscope for analyzing changes in apoptotic behavior of the cells. MTT assay was used to evaluate the cell killing effects, and the percentage of apoptotic cells analyzed using flow cytometry. Results After inhibition of the phospholipase C gamma1 signaling pathway by U73122, SW620 cells exhibited obvious apoptotic morphology, the viable cells decreased dramatically, and the percentage of apoptotic cells rose to above 50%. Conclusion Inhibition of phospholipase C gamma1 signaling pathway can induce apoptosis of human colorectal carcinoma cells.

CLC Number:

LIU Jun, LI Ming, ZENG Wei-sen, BAI Xiao-chun, LUO Shen-qiu. Inhibition of phospholipase C gamma1 signaling pathway promotes apoptosis of human[J]. Journal of Southern Medical University, 2005, 25(02): 177-180.

References

[1] Deb TB, Coticchia CM, Dickson RB, et al. Calmodulin-mediated activation of Akt(PKB) regulates survival of c-Myc-overexpressing mouse mammary carcinoma cells[J]. J Biol Chem, 2004, 279(37):38903-11.
[2] JiQS, WinnierGE, NiswenderKD, etal. Essential role of the tyrosine kinase substrate phospholipase C gammal in mammalian growth and development[J]. Proc Natl Acad Sci USA, 1997, 94(7):2999-3003.
[3] Liao HJ, Kume T, Mckay C, et al. Absence of erythrogenesis and vasculogenesis in phospholipase c gammal deficient mice [J]. J Biol Chem, 2002, 277(11): 9335-41.
[4] LeeYH, KimS, Kim J, et al. Overexpressionofphospholipase C-gammal suppresses UVC-induced apoptosis through inhibition of c-fos accumulation and c-Jun N-terminal kinase activation in PC12 cells[J]. Biochim Biophys Acta, 1999, 1440(2-3): 235-43.
[5] Bai XC, Liu AL, Deng F, et al. Phospholipase C-gammal is required for survival in heat stress: involvement of protein kinase C-dependent Bcl-2 phosphorylation [J]. J Biochem, 2002, 131(2): 207-12.
[6] Park DI, Choi HY, Kam CW, et al. Wikyungtang inhibits proliferation of A549 human lung cancer cells via inducing apoptosis and suppressing cyclooxygenase-2 activity [J]. Oncol Rep, 2004, 11(4): 853-6.
[7] Woo JH, Kim YH, Choi YJ, et al. Molecular mechanisms of curcumin-induced cytotoxicity: induction of apoptosis through generation of reactive oxygen species, down-regulation of Bcl-XL and IAP, the release ofcytochrome c and inhibition ofAkt [J].Carcinogenesis, 2003, 24(7): 1199-208.
[8] Yeo JK, Cha SD, Cho CH, et al. Se-methylselenocysteine induces apoptosis through caspase activation and Bax cleavage mediated by calpain in SKOV-3 ovarian cancer cells [J]. Cancer Lett, 2002, 182(1): 83-92.
[9] Noh DY, Lee YH, Kim SS, et al. Elevated content ofphospholipase C-gamma 1 in colorectal cancer[J]. Cancer, 1994, 73(1): 36-41.
[10] Smith MR, Lin YL, Kim H, et al. Inhibition of serum-and rasstimulated DNA synthesis by antibodies to phospholipase C [J]. Science, 1990, 247(4946): 1074-7.
[11] Mario J, Rebecchi BP, Srinivas N, et al. Structure, function, and control ofphosphoinositide-specific phospholipase C [J]. Physiol Rev, 2000, 80(4): 1291-335.
[12] Stephane M, Alexandra C, Isabelle P, [J]. Kit signaling inhibits the sphingomyelin-ceramide pathway through PLC gammal: implication in stem cell factor radioprotective effect [J]. Blood,2002, 100(4): 1294-301.
[13] Mai HQ, May WS, Gao FQ, et al. A functional role for nicotine inBcl2 phosphorylation and suppression of apoptosis [J]. J Biol Chem, 2003, 278(3): 1886-91.