title: Chemical composition of total flavonoids from Polygonum amplexicaule and their pro-apoptotic effect on hepatocellular carcinoma cells: Potential roles of suppressing STAT3 signaling.
abstract: Polygonum amplexicaule D. Don var. sinense Forb (P. amplexicaule) is a medical plant traditionally used in the treatment of malignant diseases including hepatocellular carcinoma (HCC), but the scientific basis underlying its anti-HCC activity remains poorly understood. Here, we explored the chemical profile of total flavonoids from P. amplexicaule (TFPA). Nine compounds that constituted the major components of TFPA were separated and identified. Further investigations revealed that TFPA dose-dependently induced HepG2, Huh-7 and H22 HCC cell apoptosis. In HCC cells, TFPA dramatically inhibited the transcriptional activity of signal transducer and activator of transcription 3 (STAT3). In addition, TFPA increased the expression of SHP-1, a protein tyrosine phosphatase catalyzing STAT3 dephosphorylation, in HCC cells. Animal studies showed that TFPA considerably provoked transplanted H22 cell apoptosis with undetectable toxicological effects on tumor-bearing mice. Consistently, TFPA dose-dependently inhibited transcriptional activity of STAT3 in transplanted tumor tissues. This study collectively demonstrated that TFPA has the capacity of inducing HCC cell apoptosis both in vitro and in vivo with low toxic effects on normal hepatocytes and vital organs of tumor-bearing mice. Suppressing STAT3 signaling is implicated in TFPA-mediated HCC cell apoptosis.
authors.affiliation: College of Pharmacy, South-Central University for Nationalities, Wuhan, China.
authors.forename: Meixian
authors.initials: M
authors.lastname: Xiang
authors.affiliation: Renmin Hospital, Wuhan University, Wuhan, China.
authors.forename: Hanwen
authors.initials: H
authors.lastname: Su
authors.affiliation: College of Pharmacy, South-Central University for Nationalities, Wuhan, China.
authors.forename: Zongguo
authors.initials: Z
authors.lastname: Hong
authors.affiliation: College of Pharmacy, South-Central University for Nationalities, Wuhan, China.
authors.forename: Tianming
authors.initials: T
authors.lastname: Yang
authors.affiliation: College of Pharmacy, South-Central University for Nationalities, Wuhan, China. Electronic address: shuguangwen@whu.edu.cn.
authors.forename: Guangwen
authors.initials: G
authors.lastname: Shu
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D028502:Polygonum / Q000737:chemistry*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D005419:Flavonoids; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse
keywords: Apoptosis; Flavonoids; Hepatocellular carcinoma; STAT3