The novel phospholipase C activator, m-3M3FBS, induces apoptosis in tumor cells through caspase activation, down-regulation of XIAP and intracellular calcium signaling.
We investigated the effect of the novel phospholipase C activator, m-3M3FBS, on the apoptosis of human renal Caki cancer cells. Treatment with m-3M3FBS induced apoptosis of Caki cells, which was accompanied by accumulation of sub-G1 phase and DNA fragmentation. We found that induction of apoptosis is a common response of several cancer cell types to m-3M3FBS treatment. Overexpression of Bcl-2 and c-FLIPs fails to block m-3M3FBS-induced apoptosis. However, ectopic expression of XIAP partly inhibits m-3M3FBS-induced apoptosis in Caki cells. m-3M3FBS-induced apoptosis appeared to involve the XIAP down-regulation and caspase activation. m-3M3FBS also induced the expression of a potential proapoptotic gene, C/EBP homologous protein (CHOP), however, suppression of CHOP expression by small interfering RNA did not abrogate the m-3M3FBS-induced apoptosis. In addition, inhibition of phospholipase C (PLC) or chelation of intracellular calcium prevented m-3M3FBS-induced apoptosis in Caki cells, suggesting that the involvement of PLC pathway and intracellular calcium signaling on the apoptosis in m-3M3FBS-treated Caki cells. Collectively, our present results suggest that m-3M3FBS-induced apoptosis in Caki cells may result from the activation of caspase, down-regulation of XIAP and intracellular Ca(2+) release pathway and that m-3M3FBS treatment might overcome the anti-apoptotic effect of Bcl-2 or c-FLIPs in cancer cells.
Jung
Eun Mi
EM
Department of Immunology and Chronic Disease Research Center and Institute for Medical Science, School of Medicine, Keimyung University, 194 DongSan-Dong Jung-Gu, Taegu, South Korea.
Lee
Tae-Jin
TJ
Park
Jong-Wook
JW
Bae
Yoe-Sik
YS
Kim
Sang Hyun
SH
Choi
Yung Hyun
YH
Kwon
Taeg Kyu
TK
D017209:Apoptosis / Q000187:drug effects*; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D053938:DNA Fragmentation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000494:pharmacology*; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology*; D051742:Transcription Factor CHOP / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism*; D000096926:Benzenesulfonamides
D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D020169:Caspases; D020536:Enzyme Activators; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D013449:Sulfonamides; D051742:Transcription Factor CHOP; D010738:Type C Phospholipases; D051636:X-Linked Inhibitor of Apoptosis Protein; C473783:2,4,6-trimethyl-N-(meta-3-trifluoromethylphenyl)benzenesulfonamide; D000096926:Benzenesulfonamides; C506386:CFLAR protein, human; C497249:DDIT3 protein, human