Cooperative cytotoxicity of methyl jasmonate with anti-cancer drugs and 2-deoxy-D-glucose.
The anti-cancer agent methyl jasmonate (MJ) acts in vitro and in vivo against various cancer cell lines, as well as leukemic cells from chronic lymphocytic leukemia (CLL) patients. Given the importance of multi-agent combinations in cancer chemotherapy, the purpose of this study was to identify super-additive combinations of MJ and currently-available chemotherapeutic drugs. We identified such cooperative effects in six cell lines arising from different major types of malignancies, i.e., breast, lung, prostate and pancreas carcinomas as well as leukemia. The chemotherapeutic drugs tested were adriamycin, taxol, BCNU and cisplatin. For instance, MJ exhibited strong cooperative effects with BCNU in MIA PaCa-2 pancreatic carcinoma cells. Furthermore, MJ enhanced significantly (pV=0.028) the anti-leukemic effect of adriamycin in vivo, in a CLL mouse model. Finally, MJ cooperated with the glycolysis inhibitor 2-deoxy-D-glucose in inducing death of several types of carcinoma cells. We conclude that administration of MJ with common chemotherapeutic drugs and glycolysis inhibitors bears a promise for effective anti-cancer therapy.
Heyfets
Alina
A
Department of Human Microbiology, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv 69978, Israel.
Flescher
Eliezer
E
D000085:Acetates / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003517:Cyclopentanes / Q000494:pharmacology*; D003847:Deoxyglucose / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D051379:Mice; D054883:Oxylipins
D000085:Acetates; D000970:Antineoplastic Agents; D003517:Cyclopentanes; D054883:Oxylipins; C072239:methyl jasmonate; D003847:Deoxyglucose