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 µg/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 timedependent 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 G 2 /M phase of cell cycle, DNA damageinduced 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.
Colon cancer is the third most common neoplasm worldwide and one of the major causes of death. Thus, major objective of present investigation was to identify and assess a natural molecule available in dietary sources which can sensitize colon carcinoma cells following radiation exposure. HCT-15 and RKO cells were pretreated (-30min) with silymarin followed by radiation (2 and 2.5Gy) exposure and samples were collected, analyzed at different time intervals (0-48 hrs in relation to radiation and silymarin + radiation time point respectively). Expression of proteins related to ERK/ JNK and mode of cell death was measured using western blotting (γ-H2AX, PCNA, ERK/JNK). A significant activation of JNK was observed in both the cells after treatment with silymarin and radiation. In all the samples effect was higher than silymarin alone and radiation with respect to combination group. An increase in apoptosis with increase in DNA damage was found to be accompanied with decreased SOD2 levels (0-48 hr) by combination treated group. In present investigation, silymarin was found to be potent inducer of cell death through ERK/JNK pathway. Silymarin was found to sensitize cells to radiation at non-toxic concentration and sub lethal radiation dose. Silymarin is already being utilized in traditional system of medicine (homeopathy, ayurveda and Chinese system of medicine) and therefore it possesses potential utility in future for treatment of colon cancer.
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