Cytotoxic and Apoptotic-inducing Effects of Purple Rice Extracts and Chemotherapeutic Drugs on Human Cancer Cell Lines

Abstract

Pigmented rice is mainly black, red, and dark purple, and contains a variety of flavones, tannin, polyphenols,sterols, tocopherols, γ-oryzanols, amino acids, and essential oils. The present study evaluated the cytotoxic effectsof purple rice extracts (PREs) combined with chemotherapeutic drugs on human cancer cells and mechanismsof cell death. Methanolic (MeOH) and dichloromethane (DCM) extracts of three cultivars of purple rice inThailand: Doisaket (DSK), Nan and Payao (PYO), were tested and compared with white rice (KK6). Cytotoxicitywas determined by 3-(4, 5-dimethyl)-2, 5-diphenyltetrazolium bromide (MTT) assay in human hepatocellularcarcinoma HepG2, prostate cancer LNCaP and murine normal fibroblast NIH3T3 cells. MeOH-PYO-PRE wasthe most cytotoxic and inhibited HepG2 cell growth more than that of LNCaP cells but was not toxic to NIH3T3cells. When PREs were combined with paclitaxel or vinblastine, they showed additive cytotoxic effects on HepG2and LNCaP cells, except for MeOH-PYO-PRE which showed synergistic effects on HepG2 cells when combinedwith vinblastine. MeOH-PYO-PRE plus vinblastine induced HepG2 cell apoptosis with loss of mitochondrialtransmembrane potential (MTP) but no ROS production. MeOH-PYO-PRE-treated HepG2 cells underwentapoptosis via caspase-9 and-3 activation. The level of γ-oryzanol was highest in DCM-PYO-PRE (44.17 mg/g)whereas anthocyanin content was high in MeOH-PYO-PRE (5.80 mg/g). In conclusion, methanolic Payaopurple rice extract was mostly toxic to human HepG2 cells and synergistically enhanced the cytotoxicity ofvinblastine. Human HepG2 cell apoptosis induced by MeOH-PYO-PRE and vinblastine was mediated througha mitochondrial pathway.