Synthetic analogues of marine alkaloid clathrodin differently induce phosphatidylserine exposure in monocytic cancer cells then in cancer stem cell lines

Abstract

Activation of apoptosis in cancer cells could stop the development of several cancers. Through testing in different human cancer cell lines (blood, liver, pancreas) and cancer stem cell lines (pancreas and testis), a cytomic approach was performed to investigate kinetic differences in the mechanism of proapoptotic activity induced by four synthetic analogues of clathrodin-an alkaloid isolated from Caribbean sea sponge. Active on the tested cancer stem cell lines, analogue 5 interestingly shows a differential response in apoptosis induction in the presence of pan caspase inhibitor Z-VAD-fmk in monocytic THP-1 cells. Thus in monocytic cells, contrary to cancer stem cells, this caspase independent mechanism could reflect either a scramblase modulation, a disturbed bidirectional trafficking of the membrane between the surface and cytoplasm or a necroptosis induction.