EMAIL THIS PAGE TO A FRIEND

Life sciences

CKD712, a synthetic isoquinoline alkaloid, enhances the anti-cancer effects of paclitaxel in MDA-MB-231 cells through regulation of PTEN.


PMID 25058922

Abstract

It has been reported that in human glioblastoma cells, phosphotase and tensin homolog (PTEN) positive cells are more prone to paclitaxel-induced apoptosis than PTEN-negative cells. We investigated whether (S)-1-(α-naphthylmethyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (CKD712) enhances the therapeutic effects of paclitaxel (including effects on cellular proliferation, invasion and apoptosis) in MDA-MB-231 cells through PTEN and NF-κB activity. Cellular proliferation, invasion and apoptosis were assessed by MTT, Western blot analysis, and TUNEL assay. The combination of paclitaxel and CKD712 significantly decreased cell growth, invasion and MMP-9 expression/activity compared with paclitaxel alone. CKD712 enhanced the inhibition of cell growth and invasion in response to paclitaxel in scramble siRNA-transfected, but not siPTEN-transfected cells. CKD712 significantly increased the levels of apoptosis induced by paclitaxel and this apoptosis was accompanied by reduced expression of Bcl-xL but increased activation of caspase-3. TUNEL assay further confirms that CKD712 enhanced the apoptotic effect of paclitaxel. Interestingly, over-expression of PTEN decreased phosphorylation of IκBα and NF-κB expression in the nucleus, indicating that PTEN modifies NF-κB activity in MDA-MB-231 cells. CKD712 treatment also significantly reduced expression of p-IκB and NF-κB activity in TNF-α activated cells. CKD712 strongly enhances the anti-cancer effects (proliferation, invasion, and apoptosis) of paclitaxel on MDA-MB-231 cells by regulating PTEN and NF-κB activity.