Fisetin shows potential for TNBC breast cancer treatment and enhances medication impact

Triple-negative breast cancer (TNBC) refers to any breast cancer that does not express the genes for estrogen receptor (ER), progesterone receptor (PR) or Her2/neu. This makes it more difficult to treat since most chemo therapies target one of the three receptors, so triple-negative cancers often require combination therapies. Some types of triple-negative breast cancer are known to be more aggressive with poor prognosis, while other types have very similar or better prognosis than hormone receptor positive breast cancers.

Fisetin, a flavonoid found in a number of fruits and vegetables, has diverse biological activities, including cytotoxic effects on cancer cells. In this study, the researchers investigated the effect of fisetin on triple-negative breast cancer (TNBC) cells. The results showed that Fisetin inhibited the growth of cancer cell lines extracted from the mammary gland/breast tissue and pleural effusions TNBC cells, as well as their ability to form colonies. At the same time the growth of healthy cells was not substantially affected. In addition, fisetin inhibited the growth of estrogen receptor-bearing MCF-7 which is another mammary cancer cell line and human epidermal growth factor receptor 2-overexpressing SK-BR-3 mammary breast cancer cells.

In these cell lines Fisetin inhibited TNBC cell division and induced apoptosis The mechanisms are associated with mitochondrial membrane permeabilization and the activation of caspase-9 and caspase-8, as well as the cleavage of poly(ADP-ribose) polymerase-1. The induction of caspase-dependent apoptosis by fisetin was confirmed by reduced killing of TNBC cells when the researchers introduced  pan-caspase inhibitors negating the Fisetin impact. Further analyses indicated that fisetin-induced apoptosis was the result of Aurora B kinase inhibition.

Possibly even more interesting, the effectiveness of cancer drugs cisplatin, 5-fluorouracil, and cyclophosphamide on TNBC cells was increased in the presence of fisetin. Indicating that drug treatment in combination with fisetin administration or supplementation may be a strategy.

Overall the findings suggest that further investigation and testing of Fisetin is warranted for possible use in the treatment of TNBC.

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