Oocyte-based screening of cytokinesis inhibitors and identification of pectenotoxin-2 that induces Bim/Bax-mediated apoptosis in p53-deficient tumors

Deregulation of Cdk2 causes Bim-mediated apoptosis in p53-deficient tumors following actin damage

“…In addition, the sub-G 1 population significantly increased in the p53-and p21-knockout cells, but not in their parental cells (Figure 2b), supporting previous report that p53-deficient tumor cells have the enhanced sensitivity to actin-damaging drugs (Chae et al, 2005). Because populations with 16 and 32N DNA content were not less increased as compared to reduction of cells with 4 and 8N DNA content, it is likely that polyploid cells move to sub-G 1 populations.…”

“…Upon actin damage, Bim expression was induced in tumor cells lacking functional p53, but not in cells with functional p53 (Chae et al, 2005). In this study, we found the deregulation of Cdk2 in p53-deficient tumor cells caused abrogation of tetraploid G 1 checkpoint arrest and Bim-mediated apoptosis after actin damage.…”

“…We previously reported that actin damage induces Bimmediated apoptosis in p53-deficient tumors (Chae et al, 2005). In this study, we first examined whether actin inhibitors affect p53-signaling pathway.…”

“…We previously reported that loss of p53 sensitizes tumor cells to actin damage induced by treatment with actin-depolymerizing or knotting agents (Chae et al, 2005). Upon actin damage, Bim expression was induced in tumor cells lacking functional p53, but not in cells with functional p53 (Chae et al, 2005).…”

Pectenotoxin-2 induces G2/M phase cell cycle arrest in human breast cancer cells via ATM and Chk1/2-mediated phosphorylation of cdc25C

“…Previous studies have shown that PTX-2, through its binding site with actin, can modify the actin cytoskeleton by its depolymerization, in vitro and in vivo (3,4). In addition, this compound not only displays selective and potent cytotoxicity against human lung, colon and breast cancer cells, but also induces Bim/Bax-mediated apoptosis in p53-deficient tumors (5,6). It has been shown that PTX-2 can inhibit proliferation of p53-null leukemia cancer cells by causing apoptosis, followed by inhibition of actin polymerization (7).…”