Potential Chemopreventive Role of Boldine Against Hepatocellular Carcinoma via Modulation of Cell Cycle Proteins in Rat Model
| Autor: | Ashok Mari, Nirmala Subramaniam, Palanisamy Krishnan, Pugazhendhi Kannan, Devaki Thiruvengadam, Gopalakrishnan Balaraman, Sharmila Salam, Jagan Sundaram, Sathesh Kanna Velli |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Cancer Research Aporphines Carcinoma Hepatocellular Administration Oral Antineoplastic Agents Cell Cycle Proteins medicine.disease_cause chemistry.chemical_compound Cyclin D1 Cyclin-dependent kinase medicine Animals Boldine Cell Proliferation Pharmacology chemistry.chemical_classification Reactive oxygen species Lipid peroxide biology Chemistry Liver Neoplasms Cell cycle Rats Disease Models Animal Cyclin E1 Cancer research biology.protein Molecular Medicine Drug Screening Assays Antitumor Oxidative stress |
| Zdroj: | Anti-Cancer Agents in Medicinal Chemistry. 21:2546-2552 |
| ISSN: | 1871-5206 |
| DOI: | 10.2174/1871520621666210203102854 |
| Popis: | 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/Kip1, 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 establish it as a chemopreventive agent in diethylnitrosamine-induced hepatocarcinogenesis in rats. |
| Databáze: | OpenAIRE |
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