Mechanism of cannabinois-induced apoptosis in cells of immune origin
(2003) 42nd Annual Meeting of the Society of Toxicology — Location: Salt Lake City, Utah, USA
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- Abstract
- Previous studies from our laboratories have shown that ligation of cannabinoid receptor by delta 9 -tetrahydrocannabinol (THC) leads to the induction of apoptosis in normal and transformed immune cells. These data suggested that immunosuppression mediated by cannabinoids may result from induction of apoptosis and that cannabinoids can be used as novel anti-cancer agents. Here we show that JWH015, a CB2 specific agonist, exerts a similar effect on splenocytes and thymocytes in vitro. Splenocytes treated with JWH015 showed a decreased ability to proliferate in response to mitogenic stimuli. In addition treatment of both splenocytes and thymocytes with JWH015 led to the induction of apoptosis in vitro. Studies to determine the mechanism of action of JWH015 showed a decrease in mitochondrial membrane potential of thymocytes and splenocytes, suggesting the involvement of the mitochondrial pathway. Further mechanistic studies conducted in the human lymphoma cell line Jurkat showed that caspase 8-deficient and FADD-deficient cells were sensitive to decrease in the mitochondrial membrane potential thereby suggesting that the mitochondrial pathway was independent of death-receptor signaling. However, the caspase 8 deficient cells were partially sensitive to apoptosis thereby suggesting that death-receptor pathway may play a role in THC-induced apoptosis. Moreover, Western blot analysis of protein extracted from wild-type Jurkat cells treated with THC showed cleavage of both caspase 8 and caspase 9, thereby confirming the involvement of these two pathways. Together this study shows that cannabinoids induce apoptosis in cells of immune origin and that both the death receptor and the mitochondrial pathways are involved.
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Lombard, C., Nagarkatti, M., & Nagarkatti, P. (2003). Mechanism of cannabinois-induced apoptosis in cells of immune origin. Toxicological Sciences, 78(1), 65. https://hdl.handle.net/2078.5/182047 (Original work published 2003)