Dual Role of Triphala Extracts in Breast Cancer Therapy: Enhanced Paclitaxel Cytotoxicity by Ethanolic Extract and Cytoprotection by Aqueous Extract

Authors

Supamas Charucharana, Chulalongkorn UniversityFollow
Poonlarp Cheepsunthorn Ph.D., Chulalongkorn UniversityFollow
Chalisa L. Cheepsunthorn Ph.D., Chulalongkorn UniversityFollow

Abstract

Background: Combining antioxidants with chemotherapy is an emerging strategy to reduce chemotoxicity in normal cells. Triphala (TPL), a polyphenol-rich Thai herbal formulation, has shown promise in enhancing chemotherapy efficacy, but its interaction with paclitaxel (PX) in breast cancer treatment remains underexplored.

Objective: This study evaluates the effects of aqueous (TPL-w) and ethanolic (TPL-a) TPL extracts combined with low-dose PX on breast cancer cells and non-tumorigenic mammary epithelial cells.

Methods: The bioactive components of TPL-w and TPL-a were identified using high-performance liquid chromatography (HPLC). Thiazolyl blue tetrazolium bromide (MTT) and chloromethyl 2′,7′-dichlorodihydrofluorescein diacetate (CM-H₂DCFDA) assays assessed cell viability and reactive oxygen species (ROS) levels in breast cancer (MDA-MB-231, MCF-7) and epithelial (MCF-10A) cells. Combination index (CI) values were calculated with CompuSyn, while quantitative PCR (qPCR) analyzed apoptosis- and antioxidant-related gene expression.

Results: Gallic acid was the predominant compound in both extracts, with higher levels detected in TPL-a. Co-treatment with PX and TPL-a exhibited greater cytotoxicity in breast cancer cells, particularly in MDA-MB-231, compared to TPL-w, primarily through enhanced ROS accumulation (P < 0.01) and an elevated BAX/BCL2 ratio (P < 0.01), leading to apoptosis. TPL-a significantly downregulated SOD1 and GPX1 in cancer cells, amplifying oxidative stress. Conversely, TPL-w showed moderate cytotoxicity but effectively protected MCF-10A cells by upregulating SOD1 and GPX1 (P < 0.01), reducing ROS levels (P < 0.001), and lowering the BAX/BCL2 ratio (P < 0.001), enhancing cell survival.

Conclusions: TPL-a demonstrated superior anticancer activity when combined with PX, while TPL-w provide stronger cytoprotection for normal cells. These findings highlight TPL-a’s potential as complementary chemotherapeutic agent and TPL-w’s protective role warranting further investigation into their clinical applications.

DOI

10.56808/2673-060X.5598

Recommended Citation

Charucharana, Supamas; Cheepsunthorn, Poonlarp Ph.D.; and Cheepsunthorn, Chalisa L. Ph.D. (2025) "Dual Role of Triphala Extracts in Breast Cancer Therapy: Enhanced Paclitaxel Cytotoxicity by Ethanolic Extract and Cytoprotection by Aqueous Extract," Chulalongkorn Medical Journal: Vol. 69: Iss. 4, Article 3.
DOI: https://doi.org/10.56808/2673-060X.5598
Available at: https://digital.car.chula.ac.th/clmjournal/vol69/iss4/3