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

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

Volume: 21 Issue: 18

Author(s): Nirmala Subramaniam , Pugazhendhi Kannan, Jagan Sundaram, Ashok Mari , Sathesh K. Velli, Sharmila Salam, Palanisamy Krishnan, Gopalakrishnan Balaraman and Devaki Thiruvengadam*

Affiliation:

• Department of Biochemistry, University of Madras, Guindy Campus, Chennai, Tamilnadu,India

Keywords: Boldine, Diethylnitrosamine, Hepatocellular carcinoma, Antioxidants, Proliferative markers, Cell cycle proteins.

Abstract:

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., p21^Cip1/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 p21^Cip1/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.

Cite this article as:

Subramaniam Nirmala , Kannan Pugazhendhi , Sundaram Jagan , Mari Ashok , Velli K. Sathesh , Salam Sharmila, Krishnan Palanisamy , Balaraman Gopalakrishnan and Thiruvengadam Devaki *, Potential Chemopreventive Role of Boldine Against Hepatocellular Carcinoma via Modulation of Cell Cycle Proteins in Rat Model, Anti-Cancer Agents in Medicinal Chemistry 2021; 21 (18) . https://dx.doi.org/10.2174/1871520621666210203102854