Kroning R, Lichtenstein A
Department of Medicine, VA West Los Angeles Hospital and UCLA Comprehensive Cancer Center, CA 90073, USA.
Leuk Res. 1998 Mar;22(3):275-86. doi: 10.1016/s0145-2126(97)00170-7.
We investigated the in vitro effects of paclitaxel (taxol) on multiple myeloma (MM) cells. A dose- and time-dependent induction of BCL-2 phosphorylation and apoptosis was detected in MM cell lines and two fresh clinical samples obtained from patients. A p170-overexpressing MM line and a line that did not express BCL-2 were resistant. Since phosphorylation of BCL-2 inactivates its anti-apoptotic function and could theoretically sensitize MM cells to other agents, we tested combinations of taxol and dexamethasone. Only concentrations of taxol that phosphorylated BCL-2 interacted with dexamethasone for enhanced apoptotic death. Geldanamycin, which prevented taxol-induced BCL-2 phosphorylation, also prevented the potentiated cytotoxicity.
