A new study has described the molecular mechanism of action by which the flavonoid luteolin induces breast cancer cell death. Luteolin has been shown to exert anticancer activity in various types of human cancer cells. However, the underlying mechanisms are not well understood. In the study, luteolin was found to cause a decrease in breast cancer cell viability in a dose-dependent and time-dependent manner. Cell cycle measurements and staining demonstrated that luteolin induced programmed cell death (apoptosis).

In addition, luteolin was shown to induce activation of extracellular signal regulated kinase (ERK) and p38. This was confimed by the fact that pharmacological inhibition or knockdown of ERK and p38 was found to protect against luteolin-induced cell death. Further testing using immunocytochemistry demonstrated that luteolin triggers apoptosis-inducing factor (AIF) nuclear translocation, which in turn was mediated by activation of ERK and p38. This result was again supported by the fact that transfection of vector expressing microRNA of AIF prevented the luteolin-induced cell death. The authors conclude that luteolin induces a caspase-dependent and caspase-independent apoptosis involving AIF nuclear translocation mediated by activation of ERK and p38 in breast cancer cells.

Comments regarding the study

Flavonoids are plant pigments found primarily in fruits and vegetables. Like apigenin, luteolin is a flavone, a subclass of flavonoids. These two flavones are often found together in the same foods. Parsley and celery are the most abundant food sources of luteolin; it is also found in bell peppers and hot peppers, carrots, artichokes, olives and olive oil, as well as spices such as mint, rosemary, sage and thyme. Numerous studies have reported that flavones induce programmed cell death in various types of cancer cells, including breast cancer. Luteolin has also been shown increase the anti-cancer effects of the chemotherapy drugs Adriamycin (doxorubicin) and Taxol (paclitaxel). Italian population studies have reported that high dietary intake of flavones is associated with lower risk of breast cancer.