Anti-cancer activity and effect on oxidative status of caffeoylquinic acid derivatives in breast cancer cell lines

Abstract

Breast cancer is the most commonly diagnosed cancer in women worldwide. Although currently available chemotherapeutic drugs kill these cancer cells effectively, they often cause serious side effects. Previously, the crude extract from Pluchea indica tea leaves was found to be able to inhibit the proliferation of several cancer cells including those of breast, and caffeoylquinic acid (CQA) derivatives have been reported as the major phenolic compounds from P. indica tea leaves. Therefore, in the present study, the anti-cancer activity of selected CQAs was evaluated in breast cancer MCF-7 and MDA-MB-231 cells, in comparison to non-cancer Vero cells. Cytotoxicity of mono-CQAs (3-CQA, 4-CQA and 5-CQA) and di-CQAs (3,4-diCQA, 3,5-diCQA, and 4,5-diCQA) was assessed by the MTT assay. MTT result showed that mono- and di-CQAs could inhibit the growth of MDA-MB-231 than that of MCF-7 cells. Di-CQAs exerted the stronger effect than mono-CQAs and among them, 3,4-diCQA has the lowest IC50 values (108 ± 31.06 µM). In addition, all CQA derivatives had low toxic effect on Vero cells (IC50 values > 200 µM). The colony formation assay was further examined in MDA-MB-231 cells treated with di-CQAs at the IC50 concentration. The result showed that 3,5-diCQA could inhibit cancer colony formation by 23.79 % at 100 µM and 38.79 % at 200 µM. Moreover, results from a transwell assay also showed that all di-CQAs tested could suppress the migration of the breast cancer MDA-MB-231 cells by 50% - 60% at 100 µM. Finally, the redox state of cells treated with di-CQAs was examined in order to determine the role of ROS in inducing cytotoxicity by the compounds. The results from DCFDA staining assay showed that an intracellular ROS level was increased in MDA-MB-231 exposed to di-CQAs, especially 3,5-diCQA, and was relative to a reduction of cell viability. This finding suggests that the cytotoxic effect of di-CQAs was, at least, due to an induction of oxidative stress inside breast cancer cells. Overall results indicate the potential of CQAs in suppressing breast cancer cells with minimal side effect to those of non-cancer and can be developed as anticancer drugs for treatment of breast cancer.

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