Investigating the Combinational Effect of Micellar Curcumin and Metformin on the Invasion of PC3 Prostate Cancer Cell Line

Abstract

Introduction: Adverse side effects, non-specific function, and increasing tolerability of tumor cells to chemotherapy demand therapeutic strategies with fewer side effects and better efficacy. Curcumin and metformin have been shown to have anticancer properties, according to emerging research. Therefore, micellar curcumin and metformin were combined and analyzed on cancer cell line PC3. Material and Methods: Cell viability after drug treatment, individually and in combination, was evaluated using an MTT assay. In order to determine the type of interaction between micellar curcumin and metformin, the median-effect method was employed. Subsequently, the expression of MMP-2 and MMP-9 of cells treated with single drugs and a synergistic combination of compounds was assessed using Gelatin Zymography test. Moreover, evaluating the number of invasive cells under treatment with drugs alone and in combination through matrigel invasion assay. Results: The results demonstrated that the cell proliferation treated with micellar curcumin and metformin alone and in combination decreased significantly (P<0.05) during 24 and 48 h. Besides, co-treatment of compounds showed synergy within 48 h. Although all the cells treated, whether with single drugs or the synergistic combination of both, showed a decline in expressing MMP-2, MMP-9, and the number of migrated cells, the maximum reduction was seen when micellar curcumin and metformin were combined. Conclusion: This study showed that metformin and micellar curcumin together have a synergistic effect on cell proliferation inhibition in the PC3 cell line. Metformin and micellar curcumin were more effective as a combination in decreasing the PC3 cell line invasion by reducing MMP-2 and MMP-9.