Combination of Curcumin and Metformin Inhibits Cell Growth and Induces Apoptosis without Affecting the Cell Cycle in LNCaP Prostate Cancer Cell Line

Abstract

Side effects and chemotherapy resistance, demand new therapeutics with minimal side effects. Here, we investigated the combined effect of curcumin and metformin on the LNCaP prostate cancer cell line. LNCaP cells were treated with curcumin, metformin, and their combination at different concentrations. Cell viability was assessed by MTT assay and expression of Bax, Bcl-2, mTOR, hTERT, PUMA, p53 and p21 genes was analyzed by real-time PCR. Apoptosis and cell cycle were assessed by flow cytometry. Our results revealed that the viability of cells treated with curcumin, metformin, and their combination was significantly (P < 0.05) reduced with increasing the concentration and prolonging the treatment time. Meanwhile, the combination showed a synergistic effect within 48 h. In the curcumin treated group, the expression of Bcl-2 and hTERT genes diminished. In the metformin treated group, the expression of Bax and PUMA genes was enhanced while the expression of Bcl-2, hTERT, mTOR, and p53 genes declined. Although all treatments induced apoptosis, the combination of curcumin and metformin showed the maximum level of apoptosis, cytotoxicity, and expression of Bax gene. The combination of curcumin and metformin showed synergistic effects within 48 h. This combination could be a potential therapeutic candidate for prostate cancer to be further investigated.

Graphical Abstract