THE ANTI-CANCER EFFECT OF THE EXTRACT FROM DIFFERENT PARTS OF MOMORDICA COCHINCHINENSIS (LOUR.) SPRENG. AGAINST PROSTATE CANCER CELLS.

Abstract

Prostate cancer is one of the most common cancers among men, which is marked by the abnormal control of cell division in the prostate gland. Although the incidence of prostate cancer is presently declining, the number of patients in the metastatic stage has increased over the last decade. Hence, new ways of treatment especially the uses of natural products is worth studying. In the present study, Momordica cochinchinensis (MC) or Gac fruit has various biological activities and was therefore be selected for cytotoxic screening and evaluation for the ability of metastasis inhibition against prostate cancer cells. Methanol extracts from different parts of MC were firstly prepared (stems, roots, seeds, leaves, and arils) and a cytotoxic screening with MTT assay comparing between prostate cancer cells (PC-3) and representative of normal cells (Vero). The results showed that stem extract at 24 h from MC has the highest cytotoxicity and selectivity which IC50 for PC-3 cells was 0.62 mg/ml, while for Vero cells it was 2 mg/mL. The mechanism for apoptotic death induced by the stem extract was further evaluated in PC-3 cells. As a result, all characteristics were clearly observed, including nuclear cell condensation, fragmentation, accumulation of Sub-G1 population, and dissipation of mitochondrial membrane potential. In addition, stem extract could increase the amount of pro-apoptotic Noxa and caspase-3, while the anti-apoptotic both BcL-xL and McL-1 were significantly decreased. To determine the chemical composition of the stem extract, chromatographic techniques were used, in which the main constituents of the stem extract were characterized as α-spinasterol and ligballinol, as well as some fatty acids. However, to further investigate the effect of aril extract on metastasis process, especially, cell migration was performed. The IC50 of PC-3 cells were 2.01 mg/mL, 0.59 mg/mL for 48, and 72 h, differ from LNCaP cells were 0.56 mg/mL for 24 h, but at 48, and 72 h of treatment extracts, tended to induce cell proliferation. In addition, a cell damage with sonicated water extract was clearly observed by using LDH assay. The property of metastasis inhibition was examined by wound healing, transwell insert migration assay, and MMPs expression. The results demonstrated that sonicated water extract could inhibit PC-3 cell migration, and reduced MMPs, together. These results demonstrated that the stem extract of M. cochinchinensis has cytotoxic and apoptotic effects in PC-3 cells. In addition, sonicated water extract could inhibit cell proliferation, migration in PC-3 cells. These data provided basic knowledge for developing anticancer agents for prostate cancer in the future.

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