Selectivity AND MOLECULAR MECHANISM ON ANTICANCER EXTRACT Curcuma mango Val
ABSTRACT: Cancer is still a major health problem in the world, and so in Indonesia. The nowadays cancer therapies some are not effective due to the drug resistance and bad side effect to the body. Researches on the more effective and safe drug have been proceeded for cancer diseases. It has been found that the rhizome of kunir putih (Curcuma mangga Val.) contains some active compounds with cytotoxic activities to the cancer cells. Base on that discovery, some studies had been done to identify the active compounds, to find out their sensitivity to the several cancer cells and the molecular mechanism by studying the apoptotic induction, the proliferation inhibition, and the possibility for the reducing of inflamation and invansion of the cancer, as well as the its influences to the immune system stimulation. Cytotoxicity tests had been carried out to the several cancer (Raji, HeLa, SiHa, T47D, and Myeloma) and normal (Vero) cells which had been added with the destilate (essential oil) as well as the n-hexane and ethanol extracts and maserates, of the C. mangga Val. rhizome, branch rhizome and the mixture. The most potential cytotoxic isolate then to be identified its chemical content, as well as to be studied for the expressions of the p53, caspase-9, Bcl2, H-Ras, COX-2, interleukin-10, interleukin-12 and GABA, using TUNEL and immunocytochemistry tests. The results of the studies showed that: (1) The C. mangga Val. essential oil (which contains secondary metabolites) is more cytotoxic then the n-hexane and ethanol extracts and maserates; (2) The cytotoxic activity of the C. mangga Val. essential oil is sensitive the most to myeloma cells and non toxic to the Vero cells; (3) The main components of the C. mangga Val. essential oil are -myrcene and -pinene, but the anti-cancer activity is effected by the synergy of the whole oil contents (4) Anti-cancer molecular mechanism of C. mangga Val. essential oil to myeloma cell was determined through the increasing of the pro-apoptosis protein expression of p53 and caspase-9; the un-increasing of the protein which stimulate Bcl-2 and H-Ras proliferation as well as the reducing inflamation by increasing interleukin-10 and decreasing interleukin-12 expressions. The increasing of interleukin-10 has possibility to increase of the immune system. Moreover, the increasing of COX-2 will reduce the expressions of Ras-MAPK and Bcl-2, which in turn reduces the cancer cell proliferation. However there was no influence to cancer invansion was found due to the increasing of the GABA protein expression. It is concluded that the C. mangga Val. essential oil increases cancer cell apoptosis through the mitochondrial (intrinsic) pathway. Keywords: Curcuma mangga Val., anti-cancer
