We found that the treatment with CF increased the expression of p 53 and of the cell cycle regulatory proteins p21 and p27 as compared to CNTRL. p53 controls some genes in cluding c myc. By investigating c myc, we found that its ex pression is downregulated in CF treated cells as compared to the control, suggesting that p53 negatively regulates c myc. There are reports in the literature supporting our findings showing that apoptosis could be induced through downregulation of c myc in curcumin treated cancer cells. These data indicate that p53, c myc, p21 and p27 play a decisive role in CF induced apoptosis of HCT 116 and MSTO 211 cells. CF induces apoptosis through inhibition of the PI3K Akt and Bcl 2 signaling pathway We investigated the effect of CF on PI3K Akt and Bcl 2 survival pathways.
To test the status of Akt activation, the phosphorylation of Akt was measured in HCT 116 and MSTO 211 by western blot analysis. A high level of basal phosphorylated Akt was observed in both cells, and total Akt levels were found to be almost equal in HCT 116 {our website| selleckchem|selleck chemicals|selleckchem|ML323 price and MSTO 211 cells. Consequently, we examined the protein expression and phosphorylation level of p Akt after CF treatment for the indicated times in HCT 116 and MSTO 211 cells. The levels of p Akt significantly decreased following treatment with CF while total Akt levels did not change. Our experiments on Bcl 2 western blot assay in non treated and CF treated HCT 116 and MSTO 211 cells showed an evident decrease of Bcl 2 in CF treated cells. These data indicate that CF play a decisive role in the survival pathway inhibition in HCT 116 and MSTO 211 cells.
Discussion Cancer chemoprevention using natural or synthetic com pounds to prevent or suppress the development selleckchem of cancer is an area of active investigation. Many compounds be longing to diverse chemical classes have been identified as potential chemopreventive agents, including dietary con stituents, nutraceuticals, naturally occurring phytochemi cals, and synthetic compounds. Because of their safety and the fact that they are not perceived as medicine, natural compounds have created high interest for their develop ment as chemopreventive agents that may find wide spread, long term use in populations at normal risk. Chemopreventive agents function by modulating pro cesses associated with xenobiotic biotransformation, with the protection of cellular elements from oxidative damage, or with the promotion of a more differentiated phenotype in target cells.
They induce apoptosis, inhibit cel lular proliferation, affect angiogenesis and cell metabolism in various cancers, all of which are hindrances to tumor growth. It is know that cancer cells can not grow in a high oxygen environment and that the prime cause of cancer is the replacement of the normal oxygen respiration by an anaerobic cell respiration, focusing the vital importance of oxygen.