Interaction of the antiemetics ondansetron and granisetron with the cytotoxicity induced by irradiation, epirubicin, bleomycin, estramustine, and cisplatin in vitro.
At cancer treatment, the use of antiemetics are often needed due to induction of nausea and vomiting. Some antiemetics have been shown to interact with the direct cytotoxic effects. The newly developed antiemetics have, as far as we know, not been studied in this respect. In the present study, the effects of the 5-HT3 receptor antagonists ondansetron and granisetron were evaluated on the cytotoxicity, induced by irradiation, bleomycin, epirubicin, estramustine, and cisplatin using fibroblasts (V79) and lung cancer cells (P31) in vitro. Ondansetron or granisetron (10(-5) mol/l) had no effect on the survival of irradiated cells. Granisetron (10(-5) mol/l) significantly potentiated cytotoxicity of 2.5 mg/l epirubicin on fibroblasts whereas the effect of granisetron (10(-7) mol/l) on the cytotoxic effect of 25 mg/l bleomycin, and estramustine (80 mg/l) seemed additive to lung cancer cells. Ondansetron was non-interactive with the cytotoxicity induced by any of the anti-cancer drugs. Although the encountered observation with an enhancing effect of granisetron on the epirubicin-induced cytotoxicity is seen in a specific experimental situation in vitro, the fact that 5-HT3 receptor antagonists are routinely used during cancer treatment indicate that attention should be given to a possible interaction with the antineoplastic action of cancer treatment.
Behnam Motlagh
P
P
Department of Clinical Chemistry, Umeå University Hospital, Sweden.
Henriksson
R
R
Grankvist
K
K
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D000932:Antiemetics / Q000494:pharmacology*; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D001761:Bleomycin / Q000627:therapeutic use*; D002478:Cells, Cultured; D002945:Cisplatin / Q000627:therapeutic use*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D015251:Epirubicin / Q000627:therapeutic use*; D004961:Estramustine / Q000627:therapeutic use*; D005347:Fibroblasts / Q000187:drug effects / Q000528:radiation effects; D017829:Granisetron / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D017294:Ondansetron / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D000932:Antiemetics; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D001761:Bleomycin; D002945:Cisplatin; D015251:Epirubicin; D004961:Estramustine; D017829:Granisetron; D017294:Ondansetron; D012702:Serotonin Antagonists