Wogonin Stimulation of Cell Death and Reducing Survivin in MDM-MB231 Breast Tumors

Abstract

Background: Wogonin as a flavonoid compound is known for its anticancer effect through growth control, differentiation, and apoptosis. This study investigates the possible activity of wogonin in inducing cell death of breast tumors MDA-MB231. Materials and Methods: The level of cell proliferation was evaluated by MTT assay. Cycle analysis and the apoptotic rate were assessed by flow cytometry. mRNA level of Bax, Bcl-2, p53, and survivin was evaluated by real-time PCR. Western blot was utilized to assert the relative protein expression. Results: Wogonin inhibits the proliferation of MDA-MB231 over time, and in particular, wogonin can induce the arrest of phase G1 of MDA-MB231 cells. The apoptosis of wogonin was related to a remarkable decrease in Bcl-2 and survivin and an increment in p53 and Bax. Wogonin also significantly elevated the active apoptotic forms of caspase-3, -8, -9. Z-DEVD-FMK, a specific inhibitor of caspase-3, remarkably inhibits cellular apoptosis caused by wogonin. Wogonin suppresses PI3K/Akt phosphorylation and ERK-derived phosphorylation. PD98059, a specific ERK inhibitor, significantly blocked the apoptosis caused by wogonin. Also, LY294002, a specific suppressor of PI3K, remarkably elevates the cellular apoptosis caused by wogonin. Various studies demonstrated that LY294002 not only modulates the expression of the survivin gene alone but also enhances the suppression of the expression of survivin with wogonin. Conclusion: The apoptotic role of wogonin is observed by the triggering caspases and ERK and is associated with the suppressive pathways of the PI3K/Akt/survivin signal in the MDA-MB231 cells.