Molecular investigation on the efficacy of Luteolin as a potent therapeutic agent for experimentally induced Hepatocellular carcinoma in Wistar albino rats

Abstract

Luteolin is an important flavonoid with a potential anticancer effect. Luteolin, usually occurs in its glycosylated form in celery, green pepper, perilla leaf, and camomile tea, etc., and much as an aglycone in perilla seeds. Recently, a potent anticancer effect of luteolin has been shown in several experiments in vitro. A great amount of data have indicated the therapeutic benefits of luteolin against cancer. However, it remains unclear whether these benefits are similar and equally effective in both the early and advanced stages of cancer or carcinogene is. In this study, the effects of luteolin in the advanced stages of hepatocarcinogenesis has been reported using N-nitrosodiethylamine (DEN)-induced hepatocellular carcinoma (HCC) in male Wistar rats. For this experiment, rats were categorised into four groups. The rats which developed HCC, i.e., 15-16 weeks after DEN administration (post-HCC) were treated with luteolin and compared to untreated HCC-bearing rats. The levels of cancer marker enzymes viz., and#1048878;-fetoprotein and CEA which are the known serum markers for HCC and other serum and liver marker enzymes were found to decrease upon luteolin treatment compared to untreated HCCbearing rats. Luteolin stabilizes and restores the antioxidant defense system viz., GSH, CAT, SOD, GPx and GST. These antioxidant enzymes protect cells from ROS damage in DENinduced HCC. Luteolin protects the activities of liver injury and tumor markers by decreasing MDA. The antioxidant potential was further confirmed by the non-enzymatic antioxidants such as Vitamin-C, Vitamin E, GSH and MDA levels. The DEN induced treated group showed significantly decreased levels of Vitamin-C, Vitamin-E, GSH and MDA. The non-enzymatic antioxidants in the DEN induced luteolin treated rats were found to be similar to that of control (normal) rats. These findings indicated that luteolin reduces the DEN induced increased ROS generation during hepatocarcinogenesis and promotes the enzymatic and non-enzymatic antioxidant defense system..