Taxol can induce phosphorylation of BCL-2 in multiple myeloma cells and potentiate dexamethasone-induced apoptosis.
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.
Kroning
R
R
Department of Medicine, VA West Los Angeles Hospital and UCLA Comprehensive Cancer Center, CA 90073, USA.
Lichtenstein
A
A
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D016227:Benzoquinones; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D004347:Drug Interactions; D004357:Drug Synergism; D006801:Humans; D047029:Lactams, Macrocyclic; D009101:Multiple Myeloma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D011809:Quinones / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D018931:Antineoplastic Agents, Hormonal; D000972:Antineoplastic Agents, Phytogenic; D016227:Benzoquinones; D047029:Lactams, Macrocyclic; D019253:Proto-Oncogene Proteins c-bcl-2; D011809:Quinones; D003907:Dexamethasone; D017239:Paclitaxel; C001277:geldanamycin