A Combination of Curcumin from Turmeric and Alpha-linolenic Acid Shows Antagonism with MCF-7 Breast Cancer Cells in Phenol-red Free Medium

Aims: To determine the total phenols content and antioxidant capacity for turmeric and curcumin, and to assess the effect of alpha-Linolenic acid (ALA) combinations treatments on MCF-7 breast cancer cell viability and intracellular reactive oxygen species (ROS).

Study Design: In-vitro study.

Place and Duration of Study: School of Biomedical Sciences, Ulster University, Coleraine (UK) September 2015 to September 2016.

Methods: Curcumin was characterized for total phenols content (TPC) and antioxidant capacity (AOC) using Folin-Denis and ABTS (2,2′-Azino-bis (3-ethylbenzthiazoline-6-sulfonic acid diammonium salt) assays. MCF-7 cells were grown in DMEM phenol-red free medium (+ 10% charcoal stripped foetal bovine serum) and treated with curcumin, ALA or their combinations. Cytotoxicity was assessed using the sulforhodamine-B assay. Intracellular ROS was monitored using 2,7-dichlorodihydroflourescein diacetate assay.

Results: Curcumin showed 42-50 folds higher TPC and AOC compared to turmeric. Both curcumin and ALA (0-500 µM) inhibited MCF-7 cells with the 50% effective dose (EC50) equal to 32 µM (curcumin) or 117 µM (ALA). Combination of curcumin and ALA led to EC50 values of 221 µM (curcumin) and 304 µM (ALA). Isobologram analysis and values for Combination index (CI; CI>1.0) are consistent with ALA and curcumin antagonism. Changes of intracellular ROS were 20-fold higher with ALA treatment of MCF-7 compared with curcumin.

Conclusions: ALA and curcumin were each cytotoxic towards MCF-7 breast cancer cells but their combination decreases the effectiveness of each agent due to antagonistic interactions. Both ALA and curcumin produce rises in intracellular ROS for MCF-7 cells. The wider implications of such findings is that though dietary antioxidants could be beneficial on their own, antagonistic interaction with ALA, n-3 fatty acids and other ROS generating conventional anti-cancer drug could be of concern.