Pharmacological Synergism Between Cannabinoids and Paclitaxel in Gastric Cancer Cell Lines

• Published in: The Journal of surgical research 2009-07, Vol.155 (1), p.40-47
• Main Authors: Miyato, Hideyo, M.D, Kitayama, Joji, M.D., Ph.D, Yamashita, Hiroharu, M.D, Souma, Daisuke, M.D, Asakage, Masahiro, M.D., Ph.D, Yamada, Jun, M.D, Nagawa, Hirokazu, M.D., Ph.D
• Format: Article
• Language: English
• Subjects: anandamide; Antineoplastic Agents, Phytogenic - pharmacology; Antineoplastic Agents, Phytogenic - therapeutic use; Apoptosis - drug effects; Arachidonic Acids - pharmacology; Arachidonic Acids - therapeutic use; Biological and medical sciences; Cannabinoid Receptor Modulators - pharmacology; Cannabinoid Receptor Modulators - therapeutic use; Caspases - drug effects; Caspases - metabolism; Cell Cycle - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Drug Synergism; endocannabinoid; Endocannabinoids; Enzyme Activation - drug effects; gastric cancer; Gastroenterology. Liver. Pancreas. Abdomen; General aspects; Humans; Medical sciences; paclitaxel; Paclitaxel - pharmacology; Paclitaxel - therapeutic use; Polyunsaturated Alkamides - pharmacology; Polyunsaturated Alkamides - therapeutic use; Receptor, Cannabinoid, CB1 - antagonists & inhibitors; Receptor, Cannabinoid, CB1 - metabolism; Receptor, Cannabinoid, CB2 - antagonists & inhibitors; Receptor, Cannabinoid, CB2 - metabolism; Stomach Neoplasms - drug therapy; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Surgery; Tumors
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2008.06.045

Orally applicable Δ 9-tetrahydrocannabinol and its synthetic derivatives have been used as antiemetic drugs during chemotherapy in cancer patients. However, it is not well known how cannabinoids influence the effects of chemotherapeutic agents on malignant tumors. In this study, we investigated how the endogenous cannabinoid anandamide (AEA) changes the effect of paclitaxel on gastric cancer cell lines. In the human gastric cancer cell line, HGC-27, which express cannabinoid receptor 1 (CB1), AEA stimulated proliferation at concentrations under 1 μM, while it strongly suppressed proliferation through the induction of apoptosis at 10 μM. This bimodal effect was reproduced by a selective CB1 agonist, arachidonyl-2-chloroethylamide, although the effects were less marked. When AEA was used with paclitaxel, AEA at 10 μM synergistically enhanced the cytotoxic effect of paclitaxel, whereas it showed no significant effect at lower concentrations. Flow cytometric analysis revealed that addition of 10 μM AEA synergistically enhanced paclitaxel-induced apoptosis, possibly through the activation of caspase-3, -8, and -9. Our results suggest that cannabinoids could be a good palliative agent for cancer patients receiving paclitaxel.