Farnesol alleviates diethyl nitrosamine induced inflammation and protects experimental rat hepatocellular carcinoma.

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.

Potential Chemopreventive Role of Boldine Against Hepatocellular Carcinoma via Modulation of Cell Cycle Proteins in Rat Model.

BACKGROUND: To evaluate the chemopreventive potential of boldine against diethylnitrosamine (DEN) induced hepatocellular carcinoma (HCC) in Wistar albino rats. OBJECTIVE: Boldine is an alkaloid isolated from Peumus boldus. The primary active constituents of boldine exhibited several potential medicinal properties. The present study was evaluated to explore the chemopreventive agent of boldine on anti-proliferative efficacy against diethylnitrosamine (DEN) induced hepatocellular carcinoma (HCC) in Wistar albino rats. METHODS: The effect of boldine on cellular proliferative markers, i.e., PCNA and Ki67on hepatocellular carcinoma rats was determined by immuno expression study. Liver marker enzymes, tumor biomarker, oxidative stress markers, antioxidant status, and xenobiotic phase I and II enzymes in HCC rats were analyzed. Moreover, cell cycle proteins, i.e., p21Cip1/Kip1and p27 Cip1/Kip1, Cyclin D1, CDK 4, Cyclin E1, and CDK 2 were investigated using immuno expression analysis. RESULTS: Treatment of boldine protected the liver against reactive oxygen species such as hydrogen peroxide, superoxide, protein carbonyl, and lipid peroxide during hepatocarcinogenesis by boosted antioxidants-superoxide dismutase (SOD), catalase (CAT). Boldine caused a substantial enhanced detoxification process by moderating phase I and II xenobiotic-metabolizing enzymes. Besides, the study found that boldine significantly inhibited the cellular proliferative markers like PCNA and Ki67 and regulated the specific cell cycle-associated proteins by up-regulated expression of p21Cip1/Kip1and p27 Cip1/Kip1 and down-regulated expression of Cyclin D1, CDK 4, Cyclin E1, and CDK 2. CONCLUSION: Our data manifests the anti-proliferative effect of boldine, which negatively modulates cellular proliferation and regulates cell cycle by protecting the cell from reactive oxygen species (ROS), suggesting that boldine establishes it as a chemopreventive agent in diethylnitrosamine-induced hepatocarcinogenesis in rats.

Carvacrol Promotes Cell Cycle Arrest and Apoptosis through PI3K/AKT Signaling Pathway in MCF-7 Breast Cancer Cells.

OBJECTIVE: To examine the role of carvacrol in modulating PI3K/AKT signaling involved in human breast cancer pathogenesis using in vitro experimental model MCF-7 cells. METHODS: MTT and lactate dehydrogenase assays were performed with cells treated with different doses of carvacrol (0-250 p mol/L) at different time points (24 and 48 h). The nuclear morphology was assessed in MCF-7 cells with propidium iodide (PI) and acridine orange/ethidium bromide (AO/EB) staining and analyzed by fluorescence microscopy. Events like cell cycle arrest, apoptosis was observed by flow cytometric analysis and expressions of p-Rb, cyclin D1, cyclin-dependent kinase 4 (CDK4), CDK6, Bax, Bcl-2, PI3K/p-AKT was analyzed by immunoblot. RESULTS: Carvacrol significantly reduced cell viability with the half maximal inhibitory concentration value of 200 µmol/L at 24 and 48 h (P<0.05). importantly, there was a significant increase in the accumulation of the G0/G1 phase upon treatment with carvacrol in MCF-7 cells (P<0.05 or P<0.01). A remarkable decrease in protein expressions of p-Rb, cyclin D1, CDK4 and CDK6 denotes cell cycle arrest (P<0.05 or P<0.01). In addition, carvacrol treatment significantly inhibited PI3K/p-AKT protein expressions leading to induction of apoptosis mediated by decreased Bcl2 and increased Bax protein expressions. Further, Annexin V/PI staining by FACS analysis, dual staining by AO/EB and PI staining studies suggests induction of apoptosis by carvacrol through PI3K/Akt signaling pathway in MCF-7 cells. CONCLUSION: Carvacrol significantly inhibited the breast cancer MCF-7 cell proliferation and induced apoptosis via suppressing PI3/AKT signaling pathway.

Citral inhibits N-nitrosodiethylamine-induced hepatocellular carcinoma via modulation of antioxidants and xenobiotic-metabolizing enzymes.

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.

Protective effect of vanillic acid against benzo(a)pyrene induced lung cancer in Swiss albino mice.

Vanillic acid (VA) is found in high concentrations in various plants and used as traditional medicine for various diseases. The aim of the existing study is to illustrate the protective effects of VA against benzo(a)pyrene (B(a)P)-induced lung cancer in Swiss albino mice. B(a)P (50 mg/kg b.wt.) was given orally to induce lung cancer in mice. The body weight, tumor incidence, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and enzymatic/nonenzymatic antioxidants (superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase, and glutathione) were estimated. Further histochemical investigation through hematoxylin and eosin staining was also carried out. B(a)P administered groups showed increased levels of serum pathological markers CEA, NSE along with reduced final body weight as well as decreased tissue enzymatic and nonenzymatic antioxidants activities, whereas VA treatment (200mg/kg/b.wt) along with B(a)P showed significantly reverted the above changes, which proves as prominent anticancer effects in experimentally induced lung cancer. Overall, these results suggest that VA has an efficient preventive action against B(a)P-induced lung cancer, and this is attributed to its free-radical scavenging antioxidant activities.