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Vol. 293, Issue 3, 807-812, June 2000

Cannabinoids Protect Cells from Oxidative Cell Death: A Receptor-Independent Mechanism1

Yanqiu Chen and Jochen Buck

Department of Pharmacology, Joan & Sanford I. Weill Medical College of Cornell University, New York, New York

Serum is required for the survival and growth of most animal cells. In serum-free medium, B lymphoblastoid cells and fibroblasts die after 2 days. We report that submicromolar concentrations of Delta 9-tetrahydrocannabinol (THC), Delta 8-THC, cannabinol, or cannabidiol, but not WIN 55,212-2, prevented serum-deprived cell death. Delta 9-THC also synergized with platelet-derived growth factor in activating resting NIH 3T3 fibroblasts. The cannabinoids' growth supportive effect did not correlate with their ability to bind to known cannabinoid receptors and showed no stereoselectivity, suggesting a nonreceptor-mediated pathway. Direct measurement of oxidative stress revealed that cannabinoids prevented serum-deprived cell death by antioxidation. The antioxidative property of cannabinoids was confirmed by their ability to antagonize oxidative stress and consequent cell death induced by the retinoid anhydroretinol. Therefore, cannabinoids act as antioxidants to modulate cell survival and growth of B lymphocytes and fibroblasts.

1 This study was supported by National Institutes of Health Grants DK-52797 and DK-8022.

0022-3565/00/2933-0807$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 2000 by The American Society for Pharmacology and Experimental Therapeutics


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