The Exploration Of Mechanism Of Curcumin-mediated Antitumor Activity In Breast Cancer

Cancer is a worldwide disease, which causes the major public health problem. Cancer has also become the leading cause of death in China. Chemo-therapeutic treatment is an important approach for cancer therapy besides surgery and radiation treatments. Due to chemo-resistance in cancer patients, exploration of molecular mechanism of tumorigenesis and discover of new therapeutic targets are pivotal for the better treatment of human cancer. Studies have shown that SET8, one of the methyltransferase, is involved in the regulation of gene expression, cell cycle progression, tumorigenesis and metastasis. Thus, our studies were to further explore the function of SET8 in breast cancer and discover whether natural compounds could regulate SET8 expression. Moreover, we also determine how nature compounds govern the SET8 expression, leading to anti-tumor activities in breast cancer cells.Methods1. The cell proliferation was analyzed by MTT assay and colony formation assay n breast cancer cells after curcumin treatment.2. The cell apoptosis and cell cycle were analyzed by flow cytometry in breast ancer cells after curcumin treatment.3. The ability of migration and invasion was analyzed by wound-healing assay nd Transwell assay in breast cancer cells after curcumin treatment.4. The mRNA levels of key tumorigenic genes including SET8 were analyzed by T-PCR and q-PCR in breast cancer cells after curcumin treatment.5. The expression of key proteins involved in tumorigenesis including SET8 was etected by Western blotting in breast cancer cells after curcumin treatment.6. Transfection of SET8 plasmid or small interfering RNA(siRNA) was used toregulate the expression of SET8 in breast cancer cells, and then explore themolecular mechanisms of inhibition effect of curcumin in the breast cancerdevelopment and progression.Results1. The survival and proliferation of breast cancer cells were significantly nhibited by curcumin, and this inhibitory effect was in a dose-dependent manner.2. Curcumin significantly induced apoptosis in breast cancer cells;3. Curcumin effectively blocked cell cycle progression of breast cancer cells, and rrested cell cycle at G2/M phase;4. The capacity of migration and invasion of breast cancer cells was significant nhibited by curcumin;5. The both mRNA and protein levels of SET8 were significant down-regulated y curcumin, leading to control of its downstream molecules such as hosphorylation of p53(P-p53) and p21.6. The over-expression of SET8 in breast cancer cells had significant impacts on ell proliferation, apoptosis, cell cycle, migration and invasion, which was ntagonistic with the effect of curcumin on human breast cancer cells.7. When SET8 expression was silenced by siRNA, the functional performance of reast cancer cells was similar with curcumin treatment, indicating SET8 silence nd curcumin could have a synergistic effect.ConclusionsIn the current study, we found that: First, curcimin significantly inhibited the proliferation of breast cancer cells including MDM-MB-231 and MCF-7; second, curcumin significantly induced apoptosis in breast cancer cells, and activated p53 signaling pathway; third, curcimin blocked cell cycle progression of breast cancer cells to inhibit cell division; fourth, migration and invasion of breast cancer cells was significantly inhibited by curcumin, leading to severely limiting the transfer and spread of breast cancer. In conclusion, Curcumin exerts its anti-tumor activity in breast cancer cells. Mechanically, we found that the amount of SET8 expression is tightly downregulated in breast cancer cells with curcumin treatment. Our findings suggest that curcumin plays an anti-cancer role possibly through regulation of SET8 expression in breast cancer cells.