RESUMEN
Natural compounds have been recognized as valuable sources for anticancer drug development. In this work, different parts from Momordica cochinchinensis Spreng were selected to perform cytotoxic screening against human prostate cancer (PC-3) cells. Chromatographic separation and purification were performed for the main constituents of the most effective extract. The content of the fatty acids was determined by Gas Chromatography-Flame Ionization Detector (GC-FID). Chemical structural elucidation was performed by spectroscopic means. For the mechanism of the apoptotic induction of the most effective extract, the characteristics were evaluated by Hoechst 33342 staining, sub-G1 peak analysis, JC-1 staining, and Western blotting. As a result, extracts from different parts of M. cochinchinensis significantly inhibited cancer cell viability. The most effective stem extract induced apoptosis in PC-3 cells by causing nuclear fragmentation, increasing the sub-G1 peak, and changing the mitochondrial membrane potential. Additionally, the stem extract increased the pro-apoptotic (caspase-3 and Noxa) mediators while decreasing the anti-apoptotic (Bcl-xL and Mcl-1) mediators. The main constituents of the stem extract are α-spinasterol and ligballinol, as well as some fatty acids. Our results demonstrated that the stem extract of M. cochinchinensis has cytotoxic and apoptotic effects in PC-3 cells. These results provide basic knowledge for developing antiproliferative agents for prostate cancer in the future.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Momordica/química , Extractos Vegetales/farmacología , Tallos de la Planta/química , Antineoplásicos Fitogénicos/química , Apoptosis/genética , Biomarcadores de Tumor , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Modelos Moleculares , Estructura Molecular , Fitoquímicos/química , Fitoquímicos/farmacología , Extractos Vegetales/química , Relación Estructura-ActividadRESUMEN
Momordica cochinchinensis or gac fruit has been reported to have several biological activities, including antioxidation, anti-inflammatory, and anticancer activities. However, the effect on cancer cell metastasis has not been extensively studied. With this aim, the extract from the aril part was selected and investigated for prostate cancer cell migration. The aril extracts were prepared as boiled extract, sonicated extract, ethanol extract, and HAE (hexane:acetone:ethanol; 2 : 1 : 1) extract, while the prostate cancer cell models were PC-3 and LNCaP cells. An MTT assay was performed to compare the antiproliferative effect between prostate cancer cells and normal Vero cells. As a result, the sonicated extract had the highest efficiency in PC-3 cells, with IC50 values of 2 mg/mL and 0.59 mg/mL for 48 and 72 h, respectively, while it had less of an effect in LNCaP cells and was not toxic to normal cells. Cell damage was further confirmed using LDH and cell cycle analysis. As a result, the sonicated extract did not cause cell damage or death and only inhibited cell proliferation. The effect on cancer metastasis was further examined by wound healing, transwell migration assays, and western blotting. The results demonstrated that the sonicated extract inhibited PC-3 cell migration and decreased MMP-9 but increased TIMP-1 expression. All these results support that gac fruit is a valuable source for further development as an anticancer agent for prostate cancer patients.