A Combination Therapy with Baicalein and Taxol Promotes Mitochondria-Mediated Cell Apoptosis: Involving in Akt/ß-Catenin Signaling Pathway.

ABSTRACT

Baicalein, a major flavonoid, possesses anticancer and anti-inflammatory activity. The aim of the study is to explore the efficiency of combination therapy with baicalein and taxol, as well as the molecular mechanism on antitumor activity. Human ovarian cancer cells were treated with different concentration of baicalein for 48 h, and cell viability was determined by MTT assay. Baicalein inhibited cell proliferation of ovarian cancer cells, and IC50 value of baicalein in A2780 cells, SKOV3 cells, and OVCAR cells was 46.23, 60.68, and 38.03 µM, respectively. The ovarian cancer cells were treated with 10 µM of baicalein combined with increasing concentration of taxol for 48 h, and the results demonstrated that combination therapy with baicalein and taxol had much higher antitumor effects compared with the monotherapy. The molecular mechanisms involving in combination therapy promoted the caspase-3 activity then leading to cleavage of poly-ADP-ribose polymerase, which increased the cell apoptosis of ovarian cancer cells. Moreover, Z-VAD-FMK treatment partially decreased the baicalein-induced proliferation inhibition in human ovarian cancer cells. Furthermore, baicalein induced apoptosis through activation of the activities of caspase-3,-9, and increased cytoplasmic cytochrome C release. Importantly, baicalein inhibited the growth of A2780 cells by inhibiting Akt/ß-catenin signaling pathway. In conclusion, our result revealed that baicalein combinated with taxol at low concentrations could exert synergistic antitumor effects in ovarian cancer cells through mitochondria-mediated cell apoptosis and Akt/ß-catenin signaling pathway. Baicalein has a promising potential to be developed as an antitumor compound, and combination therapy of baicalein and taxol exhibits an antitumor potential in clinical therapy for human ovarian cancers.