Isoliquiritigenin attenuates the invasive capacity of breast cancer cells via up-regulating the tumor suppressor RECK

Breast cancer is the primary cause of cancer-related deaths in women worldwide, mainly due to tumor cell metastasis. Isoliquiritigenin (ISL), a dietary compound extracted from licorice, has been well studied for its anti-oxidant and anti-inflammatory activity, however its anti-tumor invasive capacity remains largely unknown. The RECK gene acts as a tumor suppressor due to its repressive effect on tumor cell invasion. To date, no studies have determined if ISL can induce the expression of RECK. Here, we found that ISL could efficiently attenuate the invasive capacity of breast cancer cells via up-regulating RECK protein level and down-regulating micro RNA-21 (miR-21) in a dose-and time-dependent manner. Furthermore, we firstly reported that miR-21 inhibited the expression of RECK via translation repression rather than mRNA degradation in breast cancer cells. In breast cancer cell lines MDA-MB-231 and Hs-578T exposed to ISL, restored miR-21 expression by miR-21 mimics reversed the inhibitory and inductive effects of ISL on cellular invasiveness and RECK expression, respectively. Thus, the repression of miR-21 and subsequent induction of RECK may be the anti-tumor mechanism of ISL, at least partly. The results suggest an alternative for dietary tumor intervention.