Medicinal Chemistry

Tristetraprolin (TTP) is an mRNA-binding protein that can induce mRNA degradation. It controls cell growth and factors related to tumor development by binding AU-rich elements located in the 3' untranslated region (UTR) of mRNA, leading to rapid mRNA decay. Resveratrol, which is a natural flavonoid polyphenolic compound, has been shown to exert biological activities on various human cancers. However, there are no studies assessing its effects with TTP regulation on human gastric cancer. The present novel study demonstrated that the tumor suppressing effects of resveratrol were mediated via the induction of TTP expression in gastric cancer. We found that resveratrol induced TTP mRNA and protein expression in the gastric cancer cell lines SNU484 and SNU638. Treatment with resveratrol enhanced the decaying activity of TTP on luciferase mRNA containing cIAP2, LATS2, Lin28, and E2F1 in their 3' UTR. We also confirmed that TTP was upregulated. Target genes of TTP (E2F1, LATS2, and Lin28) were downregulated by resveratrol treatment in SNU484 cells as observed in a microarray experiment. Furthermore, we observed that resveratrol affects cell proliferation, metastasis, and tumor formation in SNU484 and SNU638 cells. Overall, the results of the present study suggest that resveratrol induced the mRNA and protein levels of TTP by regulating the decay of cIAP2, LATS2, Lin28, and E2F1 mRNA. It can thus be concluded that resveratrol can be utilized as a potential therapeutic anticancer agent for treating human gastric cancer.

1-Aminobenzotriazole (1-ABT) is a pan-specific, mechanism-based inactivator of the xenobiotic metabolizing forms of cytochrome P450 in animals, plants, insects, and microorganisms. It has been widely used to investigate the biological roles of cytochrome P450 enzymes, their participation in the metabolism of both endobiotics and xenobiotics, and their contributions to the metabolism-dependent toxicity of drugs and chemicals. This review is a comprehensive evaluation of the chemistry, discovery, and use of 1-aminobenzotriazole in these contexts from its introduction in 1981 to the present.