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Induction Of The Antitumorigenic NSAID-Activated Gene (NAG-1)

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ABSTRACT

Non-steroidal anti-inflammatory drug (NSAID)-activated gene (NAG-1) is a transforming growth factor (TGF)-β superfamily member that has pro-apoptotic and anti-tumorigenic activities. Cannabinoids have recently been extensively studied for their anti-tumoral activity, and NAG-1 has been shown to be up-regulated by delta 9-tetrahydrocannabinol. The present study investigated whether a synthetic hexahydrocannabinol, Yong-8, influences NAG-1 expression and apoptosis in human colorectal cancer cells, HCT-116 (wild-type p53) and HT-29 (p53 mutant). Yong-8 induced NAG-1 protein and mRNA expressions in both cell lines. Concomitantly, Yong-8 induced apoptosis of both HT-29 and HCT-116 in a concentration-dependent manner. Interestingly, Yong-8 increased p53 protein expression in both cell lines irrespective of their p53 status. Moreover, inhibition of p53 using antisense oligonucleotide caused a significant decrease in NAG-1 protein expression and apoptosis in both cell lines under the same conditions. The present study demonstrates for the first time that Yong-8, a synthetic hexahydrocannabinol, induces apoptosis in colon cancer cells. Taken together, our results suggest that hexahydrocannabinol induces colon cancer apoptosis via up-regulation of NAG-1 expression which is regulated by p53.

Source: Induction of the antitumorigenic NSAID-activated gene (NAG-1) in synthetic hexahydrocannabinol-induced apoptosis of human colorectal cancer cells -- Cho et al. 23 (1): 761.5 -- The FASEB Journal