Flavonoids from tartary buckwheat induce G2/M cell cycle arrest and apoptosis in human hepatoma HepG2 cells.
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 G2/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 G2/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.
Key laboratory of Chemical Biology and Molecular Engineering of the Ministry of Education, Shanxi University, Taiyuan 030006, China.
Yuying
Y
Li
Key laboratory of Chemical Biology and Molecular Engineering of the Ministry of Education, Shanxi University, Taiyuan 030006, China.
Shizhao
S
Duan
Key laboratory of Chemical Biology and Molecular Engineering of the Ministry of Education, Shanxi University, Taiyuan 030006, China.
Haiyan
H
Jia
Shanxi Provincial Institute of Traditional Chinese Medicine, Taiyuan 030012, China.
Chongzhi
C
Bai
Key laboratory of Chemical Biology and Molecular Engineering of the Ministry of Education, Shanxi University, Taiyuan 030006, China lwzhang@sxu.edu.cn zhwang@sxu.edu.cn.
Liwei
L
Zhang
Key laboratory of Chemical Biology and Molecular Engineering of the Ministry of Education, Shanxi University, Taiyuan 030006, China lwzhang@sxu.edu.cn zhwang@sxu.edu.cn.
Zhuanhua
Z
Wang
D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D017931:DNA Primers; D005419:Flavonoids / Q000494:pharmacology*; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects*; D006801:Humans; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000975:Antioxidants; D017931:DNA Primers; D005419:Flavonoids; D017382:Reactive Oxygen Species
ROS; anticancer; buckwheat's flavonoids; cell cycle; p53