Flavonoids from tartary buckwheat induce G<sub>2</sub>/M cell cycle arrest and apoptosis in human hepatoma HepG2 cells

Abstract

The cytotoxicity and antioxidant activity on human hepatoma cell line HepG2 of three flavonoids homogenous compounds from tartary buckwheat seeds and bran, namely quercetin, isoquercetin, and rutin, were investigated. The total antioxidant competency detection results indicated that the antioxidant capacity of quercetin was the strongest in a biological response system. A [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay showed that quercetin exhibited the strongest cytotoxic effects against the HepG2 cell line. Flow cytometric analysis indicated that quercetin significantly increased the production of reactive oxygen species, and led to the G 2 /M phase arrest accompanied by an increase of apoptotic cell death after 48 h of incubation. Quercetin-induced cell apoptosis was shown to involve p53 and p21 up-regulation, Cyclin D1, Cdk2, and Cdk7 down-regulation. These results suggested that the induction of G 2 /M arrest, apoptosis, and cell death by quercetin may associate with increased expression of p53 and p21, decrease of Cyclin D1, Cdk2, and Cdk7 levels, and generation of reactive oxygen species in cells. This study will help to better understand and fully utilize medicinal resources of plant flavonoids.

Quercetin exerts preferential cytotoxic effects on malignant mesothelioma cells by inducing p53 expression, caspase-3 activation, and apoptosis

“…The p53 leads to inhibition of cell growth by resulting in cell cycle arrest in either the g2/M or G0/G1 phase of the cell cycle. A similar activation of p53 along with G2/ M phase cell cycle arrest and apoptosis has also been observed in the case of quercetintreated several can cer cells such as hepatoma cells 23 and cervical cancer cells 6 . Unlike many other types of cancer cells which promote cell proliferation and evade apoptosis as a result of a mutant p53 gene, most of MM cells have the wildtype p53 gene but exhibits reduction in the p53 level and its activity, primarily due to a homolo gous deletion at the INK4A/ARF locus containing the p14 ARF and the p16 INK4A genes 24,25 .…”

Natural Compounds as Modulators of Cell Cycle Arrest: Application for Anticancer Chemotherapies

“…Three flavonoids homogenous compounds from tartary buckwheat seeds and bran (e.g. quercetin, isoquercetin, and rutin) leads to the G2/M phase arrest accompanied by p53 and CDKN1A (p21) upregulation, and cyclin D1, CDK-2, and -7 downregulation [141]. Quercetin-3-methyl ether, a naturally occurring compound present in various plants, has potent anticancer activity [142].…”

Athyrium multidentatum (Doll.) Ching extract induce apoptosis via mitochondrial dysfunction and oxidative stress in HepG2 cells

“…Mitochondria play a critical role in the regulation of various apoptotic processes, including drug-induced apoptosis 28 . Bcl-2 family members, such as pro-apoptotic protein Bax and anti-apoptotic protein Bcl-2 are critical regulators of the mitochondrial pathway 29, 30 . They can modulate the mitochondrial outer membrane permeability to control the release of mitochondrial cytochrome c 31 .…”