Octyl Gallate and Gallic Acid Isolated from Terminalia bellirica Circumvent Breast Cancer Progression by Enhancing the Intrinsic Apoptotic Signaling Pathway and Elevating the Levels of Anti-oxidant Enzymes

Area of Science:

• Biochemistry
• Pharmacology
• Oncology

Background:

• Breast cancer remains a leading cause of mortality globally, necessitating the development of novel, cost-effective chemoprevention strategies.
• Natural products offer a promising avenue for discovering new therapeutic agents with potentially fewer side effects.
• Terminalia bellirica is a medicinal plant with a history of traditional use, suggesting potential bioactive compounds.

Purpose of the Study:

• To evaluate the chemopreventive efficacy of octyl gallate (OG) and gallic acid (GA), isolated from T. bellirica, against breast cancer.
• To investigate the molecular mechanisms underlying the anti-cancer effects of OG and GA in breast cancer cell lines and an animal model.
• To assess the potential of OG and GA as natural chemotherapeutic agents for breast cancer prevention.

Main Methods:

• In vitro studies using breast cancer cell lines (MCF-7 and MDA-MB-231) to analyze apoptosis-related protein expression via Western blot.
• In vivo studies using a 7,12-dimethylbenz(a)anthracene (DMBA)-induced Sprague-Dawley rat model of breast cancer.
• Assessment of body weight changes, hematological indices, tumor markers (CEA, CA 15.3), oxidative stress (TBARS), and antioxidant enzyme activity (SOD, CAT, GPx) in the animal model.
• Computational molecular interaction studies and tissue histology to further elucidate the therapeutic mechanisms.

Main Results:

• OG and GA significantly altered apoptotic protein expression in breast cancer cell lines, downregulating Bcl-2 and Bcl-xL while upregulating Bak and Bax.
• In the DMBA-induced rat model, OG and GA administration led to normalized body weight and hematological profiles.
• Treatment with OG and GA significantly reduced serum tumor markers (CEA, CA 15.3) and oxidative stress (TBARS), while restoring antioxidant enzyme activity (SOD, CAT, GPx) in mammary tissue.
• Histological analysis confirmed the therapeutic role of OG and GA, supporting their chemopreventive potential.

Conclusions:

• Octyl gallate and gallic acid exhibit significant chemopreventive properties against breast cancer progression.
• These compounds exert their effects by modulating the intrinsic apoptotic signaling pathway.
• OG and GA demonstrate potential as natural chemotherapeutic agents for breast cancer prevention and warrant further investigation.