Therapeutic potential of hesperidin: Apoptosis induction in breast cancer cell lines

Hesperidin is a flavonoid commonly found in citrus fruits. Studies have shown that hesperidin has anti-inflammatory, analgesic, and antimicrobial properties, as well as its effectiveness in carcinogenesis. In this paper, we aim to investigate the molecular mechanisms of hesperidin-induced apoptosis in MCF-7 and MDA-MB-231 cancer cells. The inhibitory effect of hesperidin on cellular proliferation was evaluated with the MTT assay. Cell cycle analysis of hesperidin-treated cells was then performed, as well as immunocytochemical analysis of the effect on the apoptosis pathway (TUNEL, Bax, and Bcl-2 expression). Moreover, hesperidin induced cellular apoptosis in MCF-7 breast cancer cells by inhibiting Bcl-2 and enhancing Bax expression at protein levels. On the other hand, hesperidin caused apoptosis in the MDA-MB-231 breast cancer cell line, but it did not activate the Bax/Bcl-2 pathway. Hesperidin also induced cell cycle arrest at the S phase in the MCF-7 and MDA-MB-231 cell lines. These findings showed that hesperidin is a potential therapeutic candidate for preventing the progression of breast cancer. In addition, hesperidin could significantly stimulate the death mechanisms in ER/PR (+) MCF-7 cells by changing the expression balance of Bax and Bcl-2 proteins, but lead ER/PR (−) MDA-MB-231 breast cancer cells to apoptosis in a different way.