An improved anticancer effect of 5-fluorouracil (5-FU) in combination with Prodigiosin

Abstract 5-fluorouracil (5-FU) is the standard of care therapy for colorectal cancer. However, complex 5-FU resistance mechanisms limit the success of this approach. Prodigiosin (PG), a secondary metabolite from various bacteria, exerts different biological activities including cancer-preventive and anticancer effects. However, studies on the anticancer effects and underlying mechanisms of PG in human colorectal and lung cancer are still limited. The present study is conducted to investigate the anticancer properties and/or adjuvant chemotherapy of PG in human colorectal and lung cancer. Cell lines HCT116, LoVo and A549 were treated with different concentrations of PG. The antiproliferative effects of PG were measured, and the apoptosis and cell cycle dynamics were assessed by flow cytometry. Our results showed that PG effectively inhibited cell proliferation and induced apoptosis. In combinatory treatment, based on PG and 5-FU, we observed a clear improvement in tumor cell proliferation inhibition. In fact, the percentage of cells in the G0/G1 phase was higher and the percentage of cells in the S phase was lower compared to treated cells separately by PG and 5-FU in all the used cell lines. Our docking studies supported targeting Akt1 by PG which could explain its proapoptotic effect separately or in combination with 5-Fu. PG obviously inhibited the tumor growth and enhanced the 5-FU therapeutic efficacy in HCT116, LoVo and A549 cells. Taken together, our findings highlight that PG effectively inhibited the growth of tumor and enhanced the sensitivity to thermotherapy, indicating PG is an inhibitor of Akt1.