Studies on radiation sensitization efficacy by silymarin in colon carcinoma cells

Abstract

Recent reports demonstrated the role of silymarin as a cytoprotective agent for normal cells against ionizing or non-ionizing (UV) radiation, and in inhibiting the chemically initiated or promoted carcinogenesis in several malignancies, such as skin or prostate cancers. Silymarin is a plant flavonoid obtained from milk thistle; the main active principles in milk thistle are silybin (silibinin), sylichrisitin and silydianin, commonly referred as silymarin. In the present study, we aimed to investigate the radiation modulatory effects of silymarin on cancer cells. For this, we used the HCT-15 and RKO colon cancer cell lines as a model. Pre-irradiation treatment of cells with silymarin (20 mg/ml) followed by radiation exposure inhibits colon cancer cell proliferation and enhances cell death in a time-dependent manner. We have also examined the changes in p53 phosphorylation at Ser15, phosphorylation of p38 and their association with DNA damage. Silymarin was found to reduce proliferation of the human colon carcinoma cells in a concentration and time-dependent manner. Moreover, percentage of cell death was also increased in combined treatment (20µg/ml of silymarin + radiation). Our studies indicate that the combination increases the arrest of cells in G2/M phase of cell cycle, DNA damage-induced decrease in mitochondrial membrane potential (MMP) and a decrease of the reactive oxygen species (ROS) levels, which are associated with an increase in cell death. Altogether, these results suggest that silymarin sensitizes colon cancer cells to radiation, strategy with potential for colon cancer treatment. Noteworthy, since silymarin was previously shown to confer protection against radiation in at least some types of normal tissues, additional studies are needed to further investigate the potential of silymarin in colon cancer therapy when combined with radiation, its potential protective effects on normal tissues and its mechanisms of action.