Inhibition of cancer cell growth by Tangeretin flavone in drug-resistant MDA-MB-231 human breast carcinoma cells is facilitated via targeting cell apoptosis, cell cycle phase distribution, cell invasion and activation of numerous Caspases.

Purpose: In this study, the anticancer effects of a natural flavonoid-Tangeretin, were examined against the drug-resistant MDA-MB-231 breast cancer (BC) cell line and the normal breast cell line Hs 841.T.

Methods: The MTT assay was employed for cell viability determination. Apoptosis was demonstrated by DAPI and Annexin V/propidium iodide (PI) staining. Flow cytometric analyses were performed to gain insights about cell cycle distribution. Western blot assay was used for protein expression determination.

Results: Tangeretin inhibited the growth of the drug-resistant MDA-MB-231 cells concentration-dependently and its IC50 was 9 µM, whereas the IC50 was >100 µM against the normal cells. The anti-proliferative effects were due to induction of apoptotic cell death. The apoptotic cell percentage was increased from 5.7% to around 69% as the concentration of Tangeretin was increased. Tangeretin also caused an increase in the Bax/Bcl-2 ratio and activation of the Caspase 3, 8 and 9. In addition, Tangeretin led to arrest of the cells at G2/M phase which was accompanied by depletion of cyclin B1 and D. Transwell assay showed that Tangeretin also reduced the invasion of the MDA-MB-231 cells.

Conclusion: The findings of this study suggest that Tangeretin exerts potent anticancer effects on the MDA-MB-231 cells and may therefore prove a beneficial lead molecule in BC research.