Theophylline enhances berberine induced cell death through inducing G2/M cell cycle arrest in MDA-MB-231 cells

Introduction and Aim: Breast cancer is the most frequently recognized cancer in women worldwide. Although chemotherapy is the major therapy in breast cancer, the most of breast cancer patients experience serious side effects, demanding novel therapeutic agents are needed for breast cancer treatment. The plant-based alkaloid berberine exerts anticancer effects on various cancer cell lines. The methylxantine, theophylline, has been used for the treatment of airway disease. Theophylline inhibits enzyme phosphodiestrase, thereby increasing intracellular cAMP. In this study the effect of berberine alone and in combination with theophylline on cell growth, colony formation and cell cycle distribution in MDA-MB-231 breast cancer cells was investigated. Methods: The cells cultured in the absence and presence of berberine alone and in combination with theophylline and the viability determined by MTT assay. Flow cytometric was used to evaluate cell cycle and apoptosis. Also the ability of the cells to produce colony was examined by colony formation assay. Results: MTT assay showed that berberine treatment inhibited cell survival in a dose dependent manner and IC50was 100 µM, whereas theophylline in combination with berberine decreased IC50 to 50 µM. PI staining of the cells after berberine treatment represented arrest of the cells in G0/G1 phase, whereas combination of drugs induced G2/M arrest. Colony formation assay revealed that combination of berberine with theophylline markedly suppressed colony formation abilities of MDA-MB-231 cells, compared with berberine alone. Conclusion: Theophylline enhances berberine toxicity and sensitivity of MDA-MB-231cells, suggesting that this combination could be a new strategy for treatment of breast cancer.

کلیدواژه ها:

Berberine ، Theophylline ، MDA-MB-231 breast cancer cells