Dual role of Triphala extracts in breast cancer therapy: Enhanced paclitaxel cytotoxicity by ethanolic extract and cytoprotection by aqueous extract

Supamas  Charucharana; Poonlarp  Cheepsunthorn; Chalisa  Louicharoen Cheepsunthorn

Authors

Supamas Charucharana Medical Sciences Program, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand andFaculty of Sciences and Technology, Phranakhon Rajabhat University, Bangkok, Thailand
Poonlarp Cheepsunthorn Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
Chalisa Louicharoen Cheepsunthorn Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

Keywords:

Antioxidant therapy, breast cancer, chemotherapy, gallic acid, paclitaxel, reactive oxygen species, synergistic effect, triphala

Abstract

Background: Combining antioxidants with chemotherapy is an emerging strategy for reducing chemotoxicity in normal cells. Triphala (TPL), a polyphenol-rich Thai herbal formulation, has exhibited potential in enhancing chemotherapy efficacy; however, its interaction with paclitaxel in breast cancer treatment remains underexplored.

Objective: This study aimed to evaluate the effects of aqueous (TPL-w) and ethanolic (TPL-a) TPL extracts in combination with low-dose paclitaxel on breast cancer and non-tumorigenic mammary epithelial cells.

Methods: The bioactive components of TPL-w and TPL-a were identified using high-performance liquid chromatography. Thiazolyl blue tetrazolium bromide (MTT) and chloromethyl 22’ ,72’ - dichlorodihydrofluorescein diacetate (CM-H2DCFDA) assays were employed to assess cell viability and reactive oxygen species (ROS) levels, respectively, in breast cancer (MDA-MB-231, MCF-7) and epithelial (MCF-10A) cells. Combination index values were calculated using CompuSyn, whereas quantitative polymerase chain reaction was used to analyze apoptosis- and antioxidant-related gene expressions.

Results: Gallic acid was the predominant compound identified in both extracts, with higher levels detected in TPL-a. Paclitaxel and TPL-a cotreatment exhibited greater cytotoxicity in breast cancer cells, particularly in MDA-MB-231, compared with that of TPL-w cotreatment, primarily through enhanced ROS accumulation and an elevated BAX/BCL2 ratio, which led to apoptosis. TPL-a significantly downregulated superoxide dismutase (SOD1) and glutathione peroxidase (GPX1) expression in cancer cells, thereby enhancing oxidative stress. Conversely, TPL-w exhibited moderate cytotoxicity but effectively protected MCF-10A cells by upregulating the expression of SOD1 and GPX1, reducing ROS levels, and lowering the BAX/BCL2 ratio, thus enhancing cell survival.

Conclusion: TPL-a exhibited superior anticancer activity when combined with paclitaxel, whereas TPL-w provided stronger cytoprotection in normal cells. These findings highlight TPL-a’s potential as a complementary chemotherapeutic agent and TPL-w’s protective role, thereby warranting further investigation into their clinical applications.

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