Protective Effects of Pelargonidin against DMBA-Induced Mammary Tumorigenesis in BALB/c Mice through Reduced Oxidative Stress and Lipid Anomalies

Abstract

Among luminal types of breast cancers, ER + breast cancer is the most frequently diagnosed cancer globally. ER + breast cancer is commonly treated with SERM drugs that block ER to prevent ER-mediated cancerous growth. Our previous computational screening found pelargonidin (PG) can inhibit ER-signaling with potent bioactivity and satisfactory toxicological features. The present study explored the anti-tumoral prospect of PG against DMBA-induced ER + murine mammary carcinogenesis. The female BALB/c mice were divided into control (A) and DMBA-exposed groups. Following tumor appearance, the DMBA-exposed group was divided into five groups: tumor control, PG-treated (Groups P25, P50, and P100), and tamoxifen-treated (TAM). The results indicated that PG-treatment dose-dependently reduced the mean tumor volume, reinstated body weight loss, and enhanced the percentage survival of tumor-bearing mice. In addition, we recorded a significant reduction in LPO, total cholesterol, and triglycerides and a surge in the activity of antioxidases and phase II detoxifying enzymes in PG-treated animals. PG also dose-dependently increased the serum level of unbound estradiol, an indicator of competitive ER binding by an ER agonist/antagonist. These data suggest that pelargonidin has potent anticancer potential against the animal model of ER + breast cancer that matches the efficiency of tamoxifen with conceivably fewer side effects.

Acknowledgments

All the authors are grateful to the UGC-SAP initiative for providing laboratory infrastructure. The first author acknowledges the UGC-AUS Non-NET fellowship from the University Grants Commission, Government of India, through Assam University, for doctoral research. MN receives the DST-INSPIRE fellowship from the Department of Science & Technology, Government of India.

Disclosure Statement

All the authors declare no conflict of interest regarding this manuscript.

Data Availability Statement

The authors confirm that the data supporting the findings of this study are available within the article.

Authors Contribution

YBL: Conception; Study Design; All Experiments; Acquisition of Data; Analysis and Interpretation; Primary Manuscript Drafting; Statistical Analysis. KB: Some Experiments; Analysis and Interpretation. MN: Some Experiments; Analysis and Interpretation. YC: Critical Review; Scrutiny; Analysis and Interpretation. PBM: Conception; Study Design; Project Administration; Critical Review; Scrutiny; Analysis and Interpretation; Communication. ADT: Critical Review; Scrutiny.

Additional information

Funding

The histological studies were partially funded by the Department of Biotechnology, Government of India, through research grant sanction no. BT/567/NE/U-EXCEL/2016 dated 31st March 2017 to YC.