Faculty Bibliography

Vanadium, a dietary micronutrient, is yet to be established as an essential part of the human diet. Over the past century, several biological effects of vanadium, such as insulin-mimetic action as well as amelioration of hyperlipidemia and hypertension, have been discovered. This transition element is known to influence a battery of enzymatic systems, namely phosphatases, ATPases, peroxidases, ribonucleases, protein kinases and oxidoreductases. Multiple biochemical and molecular actions of vanadium have been implicated in its inhibitory effects on various tumor cells of human origin. Successful in vitro studies over the past few decades have advanced the anticancer research on vanadium into the preclinical stage. Vanadium in several animal cancer models provides protection against all stages of carcinogenesis--initiation, promotion, and progression. This review focuses on the current advances in cancer prevention and treatment as well as early detection by vanadium compounds in preclinical animal models while pointing to possible mechanisms of such diverse beneficial effects. Clinical pharmacokinetic and potential toxicity studies on vanadium are also highlighted in this review. Supporting and challenging evidence as well as future directions of vanadium research exploring the possibility of using this dietary agent for detection, prevention and treatment of human cancers are critically discussed.

PURPOSE/OBJECTIVE:Resveratrol, present in grapes and red wine, has been found to prevent diethylnitrosamine (DENA)-initiated rat liver tumorigenesis, though the chemopreventive mechanisms are not completely elucidated. The current study was designed to explore whether the antiinflammatory properties of resveratrol play a role in its antihepatocarcinogenic action. METHODS:Liver samples were harvested from a 20-week chemopreventive study in which resveratrol (50, 100 and 300 mg/kg) was shown to inhibit DENA-induced hepatocyte nodules in Sprague-Dawley rats in a dose-responsive manner. Hepatic preneoplastic and inflammatory markers, namely heat shock protein (HSP70), cyclooxygenase-2 (COX-2) and nuclear factor-kappaB (NF-kappaB), were studied using immunohistochemical as well as Western blot techniques. RESULTS:Resveratrol dose-dependently suppressed DENA-induced increased expressions of hepatic HSP70 and COX-2. Resveratrol also attenuated the DENA-mediated translocation of NF-kappaB p65 from the cytosol to the nucleus with stabilization of inhibitory kappaB. CONCLUSION/CONCLUSIONS:The present findings indicate that resveratrol exerts chemoprevention of hepatocarcinogenesis possibly through antiinflammatory effects during DENA-evoked rat liver carcinogenesis by suppressing elevated levels of HSP70, COX-2 as well as NF-kappaB. These beneficial effects combined with an excellent safety profile encourage the development of resveratrol for chemoprevention and intervention of human HCC that remains a devastating disease.