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Hepatocellular carcinoma is a well-known internal malignancy with increased worldwide mortality. The increased progression rate is closely associated with chronic liver diseases such as cirrhosis. Chemical carcinogens cause tumor advocacy over free radical metabolites to causes numerous biochemical and molecular changes that bring oxidative stress. In addition, inflammatory cells and its growth factor promotes the progression of liver cancer through deregulates the numerous cellular signaling pathways involved in normal cellular proliferation. Plant derived phytochemicals have a better complimentary potency to defend against a wide array of free radical mediated diseases such as cancer. More recently, we have evaluated the anticancer effect of Farnesol against DEN induced hepatocellular carcinoma in male wistar albino rats. However, the possible mechanism in which Farnesol attributes its anticancer effect against DEN induced liver cancer remains unknown. Hence in the present study, an attempt has been made to reduce the oxidative stress by appraise the antioxidant effect by Farnesol in DEN induced hepatocellular carcinoma. Elevated oxidative stress markers with concomitant decreased cellular antioxidants levels were observed in DEN induced hepatic tissues. Further, proliferating nuclei with increased proliferating cell nucleolar antigen (PCNA) and inflammatory mediator expression were observed in DEN induced rats. Oral supplementation of Farnesol to DEN induced rats significantly decrease the oxidative stress markers and increase the cellular antioxidant status. Moreover, Farnesol treatment decreases the argyrophilic nuclear organizer region and PCNA along with decreased expression of inflammatory mediators suggest that Farnesol treatment restores DEN induced hepatic abnormalities and protects liver from cancer progression., (© 2021 Wiley Periodicals LLC.)

Hepatocellular carcinoma (HCC) ranks the sixth position among various cancers worldwide. Recent research shows that natural and dietary compounds possess many therapeutic effects. Citral is a monoterpene aldehyde that contains geranial and neral. The present study was considered to study the role of citral against N-nitrosodiethylamine (NDEA)-induced HCC via modulation of antioxidants and xenobiotic-metabolizing enzymes in vivo. NDEA-alone-administered group II animals profoundly showed increased tumor incidence, reactive oxygen species, liver marker enzyme levels, serum bilirubin levels, tumor markers of carcinoembryonic antigen, α-fetoprotein, proliferative markers of argyrophilic nucleolar organizing regions, proliferating cell nuclear antigen (PCNA) expressions, phase I xenobiotic-metabolic enzymes and simultaneously decreased antioxidants, and phase II enzymes levels. Citral (100 mg/kg b.w.) treatment significantly reverted the levels in group III cancer-bearing animals when compared to group II cancer-bearing animals. In group IV animals, citral-alone administration did not produce any adverse effect during the experimental condition. Based on the results, citral significantly inhibits the hepatocellular carcinogenesis through restoring the antioxidants and phase II xenobiotic-enzyme levels; thereby, it strongly proves as an antiproliferative agent against rat HCC., (© 2020 Wiley Periodicals, Inc.)

Hepatocellular carcinoma (HCC) incidence rates are increasing in many parts of the world. HCC's limited treatment remedies and the poor prognosis emphasize the importance in developing an effective chemoprevention for this disease. Here, we investigated the molecular mechanisms involved in the chemoprevention of silymarin in N-nitrosodiethylamine (NDEA)-induced rat model of HCC. Liver of the rats treated with NDEA showed higher proliferation index and glycoconjugates. NDEA treatment also increased the level of anti-apoptotic proteins with simultaneous decrease in the level of pro-apoptotic proteins along with increased accumulation of Cytochrome c in mitochondria. The carcinogenic insult also increased microsomal phase I metabolizing enzymes with a simultaneous decrease in the Phase II detoxifying enzyme glutathione-S-transferase (GST). Whereas dietary silymarin administration along with NDEA treatment significantly decreased the proliferation and down regulated the expression of anti-apoptotic proteins with simultaneously increased expression of pro-apoptotic proteins along with the release of Cytochrome c to cytosol there by activating the intrinsic apoptotic pathway. Silymarin administration also decreased the level of glycoproteins and activated the phase II detoxifying enzyme GST. These results demonstrate that suppression of HCC by silymarin in vivo involves inhibition of proliferation, activation of apoptosis, and efficient detoxification.