Antioxidant and Chemotherapeutic Synergy: Triphala Enhances Doxorubicin Cytotoxicity in Breast Cancer Cells and Reduces Toxicity in Non-Tumorigenic Cells

Authors

Supamas Charucharana, Medical Sciences Program, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.Follow
Poonlarp Cheepsunthorn Ph.D., Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.Follow
Chalisa Louicharoen Cheepsunthorn Ph.D., Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.Follow

Abstract

Background: The combining of antioxidants with chemotherapy is increasingly explored to minimize toxicity in non-cancerous cells during breast cancer treatment. Triphala (TPL), a Thai herbal compound rich in antioxidants, shows potential as a complementary candidate for breast cancer chemotherapy.

Objective: This study investigated the combined effects of TPL and low-dose doxorubicin (DOX) on human breast cancer and non-tumorigenic mammary epithelial cells.

Methods: TPL’s bioactive compounds were analyzed via high-performance liquid chromatography (HPLC). Cell viability and reactive oxygen species (ROS) levels were assessed in breast cancer (MDA-MB-231, MCF-7) and epithelial (MCF-10A) cells using thiazolyl blue tetrazolium bromide (MTT) and chloromethyl 2′,7′-dichlorodihydrofluorescein diacetate (CM-H₂DCFDA) assays in triplicate. Combination index (CI) values were determined with CompuSyn, and quantitative PCR (qPCR) evaluated mRNA expression of apoptosis- and antioxidant-related genes.

Results: Gallic acid (11.9%) was identified as the major component in TPL. The combination of TPL and low-dose DOX synergistically enhanced cytotoxicity in MCF-7 and MDA-MB-231 cells. This combination reduced the expression of antioxidant genes SOD1 and GPX1 in MDA-MB-231 (SOD1: P < 0.001, GPX1: P = 0.035), and MCF-7 (SOD1: P = 0.035, GPX1: P = 0.036), leading to increased ROS levels in MDA-MB-231 (P = 0.005) and MCF-7 (P = 0.008). Elevated ROS triggered apoptosis through an increased BAX/BCL2 ratio in MDA-MB-231 (P < 0.001) and MCF-7 (P = 0.020). Conversely, TPL displayed protective effects in non-tumorigenic MCF-10A cells by upregulating SOD1 (P = 0.031) and GPX1 (P < 0.001), reducing ROS (P = 0.002), and lowering the BAX/BCL2 ratio (P< 0.001), thereby promoting cell survival.

Conclusions: TPL, in combination with doxorubicin, effectively induces cytotoxicity in breast cancer cells while protecting non-tumorigenic cells, suggesting its potential as a complementary therapy in breast cancer treatment.

DOI

10.56808/2673-060X.5560

Recommended Citation

Charucharana, Supamas; Cheepsunthorn, Poonlarp Ph.D.; and Cheepsunthorn, Chalisa Louicharoen Ph.D. (2025) "Antioxidant and Chemotherapeutic Synergy: Triphala Enhances Doxorubicin Cytotoxicity in Breast Cancer Cells and Reduces Toxicity in Non-Tumorigenic Cells," Chulalongkorn Medical Journal: Vol. 69: Iss. 2, Article 6.
DOI: https://doi.org/10.56808/2673-060X.5560
Available at: https://digital.car.chula.ac.th/clmjournal/vol69/iss2/6