Synergistic inhibition of colon cancer cell growth by a combination of atorvastatin and phloretin.

Atorvastatin (ATST), a drug commonly used to reduce the levels of cholesterol and low-density lipoproteins, is a prospective agent for the prevention of colorectal cancer in patients with hyperlipidemia. ATST in combination with functional components is a promising strategy for cancer chemoprevention. In the present study, the growth inhibitory effect of ATST combined with phloretin (PT) on SW620 and HCT116 colon cancer cells was investigated. The results of MTT assays indicated that the combination of PT and ATST markedly reduced cell survival in both cell lines compared with PT or ATST treatment administered individually. The interaction indexes between PT and ATST, which were used to analyze their interaction pattern, were computed by the median-effect equation. The interaction indexes of each PT and ATST concentration pair were <1.0, which indicated a strong synergistic effect between the two compounds. The data obtained by flow cytometry and western blot analysis of cleaved-poly (ADP-ribose) polymerase indicated a synergistic effect resulted in apoptosis and cell cycle arrest at the G2/M checkpoint. Furthermore, combined treatment with PT and ATST markedly downregulated the expression of cyclin B and upregulated the expression of phospho-cdc2 and Myt1, which suggested that the activation of cdc2 was downregulated. This combined treatment strategy enhanced the anti-cancer activity of ATST at a relatively low dosage and suggested a possible method of preventing colorectal cancer in patients with hyperlipidemia.