The novel phospholipase C activator, m-3M3FBS, induces apoptosis in tumor cells through caspase activation, down-regulation of XIAP and intracellular calcium signaling

Eun Mi Jung, Tae Jin Lee, Jong Wook Park, Yoe Sik Bae, Sang Hyun Kim, Yung Hyun Choi, Taeg Kyu Kwon

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

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 Ca2+ release pathway and that m-3M3FBS treatment might overcome the anti-apoptotic effect of Bcl-2 or c-FLIPs in cancer cells.

Original languageEnglish
Pages (from-to)133-145
Number of pages13
JournalApoptosis : an international journal on programmed cell death
Volume13
Issue number1
DOIs
StatePublished - Jan 2008

Keywords

  • Apoptosis
  • Calcium
  • CHOP
  • m-3M3FBS
  • Phospholipase C activator
  • XIAP

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