Betulinic acid induces apoptosis and impairs migration and invasion in a mouse model of ovarian cancer

Abstract

Betulinic acid (BA) was verified to possess plenty of biological activities including anti-tumor, anti-inflammatory and so on. In our research, we studied the growth inhibition, apoptosis promotion and metastasis resistance of ovarian cancer cells by BA. The result showed that BA showed a time- and dose-dependent inhibitory effect on ovarian cancer cell lines. SKOV3 cell line proliferation has a concentration- and time-dependently, which may be inhibited by BA. Furthermore, BA inhibited the metastasis of tumor cells remarkably by inhibiting epithelial-mesenchymal transition process. Beyond that, the weight and volume of subcutaneous tumor was distinctly suppressed by administration of BA in tumor-bearing mice of SKOV3 cells. Pathological and immunohistochemical tests showed that Ki-67+ and MMP-2+ cells were dramatically decreased after BA administration, indicating that BA can not only suppress proliferation, but also inhibit migration of tumor cells. Taken together, BA can be a valuable candidate drug for the treatment of ovarian cancer. Practical applications: Betulinic acid (BA) isolated from natural plants such as fenugreek, eucalyptus bulb and mulberry has been reported with many biological activities. Results from this study revealed that in vitro and in vivo BA-induced apoptosis and inhibited migration and invasion of human ovarian cancer cells. Therefore, BA from natural plants may be developed as a potential drug for inhibition the development of ovarian cancer cells.