S-Phase Cell Cycle Arrest, and Apoptotic potential of Echium arabicum Phenolic Fraction in Hepatocellular Carcinoma HepG2 Cells

The naturally occurring compound α-pinene induces cell cycle arrest and antitumor activity. We examined effects of α-pinene on cell cycle regulation in hepatocellular carcinoma cells (HepG2) cells to establish a foundation for its development as a novel treatment for hepatocellular carcinoma (HCC). HepG2 cells treated with α-pinene exhibited dose-dependent growth inhibition as a result of G2/M-phase cell cycle arrest. Cell cycle arrest was associated with down-regulated cyclin-dependent kinase 1 (CDK1) and miR-221 levels and up-regulated levels of CDKN1B/p27, γ-H2AX, phosphorylated ATM, phosphorylated Chk2 and phosphorylated p53. Our observations are consistent with a model in which α-pinene inhibits miR221 expression, which leads to G2/M-phase arrest and activation of CDKN1B/p27-CDK1 and ATM-p53-Chk2 pathways that suppress human hepatoma tumor progression. Additionally, α-pinene was found to trigger oxidative stress and induce apoptosis of HepG2 cells. α-pinene, therefore, represents a potential chemotherapeutic compound for the treatment of HCC.

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ZBP-89 reduces the cell death threshold in hepatocellular carcinoma cells by increasing caspase-6 and S phase cell cycle arrest

Cancer Letters ◽

10.1016/j.canlet.2009.03.024 ◽

2009 ◽

Vol 283 (1) ◽

pp. 52-58 ◽

Cited By ~ 15

Author(s):

George G. Chen ◽

Ursula P.F. Chan ◽

Long-Chuan Bai ◽

King Yip Fung ◽

Art Tessier ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Cycle ◽

Cell Death ◽

Cell Cycle Arrest ◽

S Phase ◽

Carcinoma Cells ◽

Phase Cell ◽

Hepatocellular Carcinoma Cells ◽

Cycle Arrest ◽

Caspase 6

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Apoptosis Induction byPolygonum minusIs Related to Antioxidant Capacity, Alterations in Expression of Apoptotic-Related Genes, and S-Phase Cell Cycle Arrest in HepG2 Cell Line

BioMed Research International ◽

10.1155/2014/539607 ◽

2014 ◽

Vol 2014 ◽

pp. 1-13 ◽

Cited By ~ 5

Author(s):

Mohd Alfazari Mohd Ghazali ◽

Ghanya Al-Naqeb ◽

Kesavanarayanan Krishnan Selvarajan ◽

Mizaton Hazizul Hasan ◽

Aishah Adam

Keyword(s):

Cell Cycle ◽

Ethyl Acetate ◽

Antioxidant Capacity ◽

Cell Cycle Arrest ◽

Hepg2 Cells ◽

S Phase ◽

Antiproliferative Effect ◽

Phase Cell ◽

Apoptosis Induction ◽

Cycle Arrest

Polygonum minus(Polygonaceae) is a medicinal herb distributed throughout eastern Asia. The present study investigated antiproliferative effect ofP. minusand its possible mechanisms. Four extracts (petroleum ether, methanol, ethyl acetate, and water) were prepared by cold maceration. Extracts were subjected to phytochemical screening, antioxidant, and antiproliferative assays; the most bioactive was fractionated using vacuum liquid chromatography into seven fractions (F1–F7). Antioxidant activity was measuredviatotal phenolic content (TPC), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and ferric reducing antioxidant power (FRAP) assays. Antiproliferative activity was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Most active fraction was tested for apoptosis induction and cell cycle arrest in HepG2 cells using flow cytometry and confocal microscopy. Apoptotic-related gene expression was studied by RT-PCR. Ethyl acetate extract was bioactive in initial assays. Its fraction, F7, exhibited highest antioxidant capacity (TPC;113.16±6.2 mg GAE/g extract, DPPH;EC50:30.5±3.2 μg/mL, FRAP;1169±20.3 μmol Fe (II)/mg extract) and selective antiproliferative effect (IC50:25.75±1.5 μg/mL). F7 induced apoptosis in concentration- and time-dependent manner and caused cell cycle arrest at S-phase. Upregulation of proapoptotic genes (Bax,p53, andcaspase-3) and downregulation of antiapoptotic gene,Bcl-2, were observed. In conclusion, F7 was antiproliferative to HepG2 cells by inducing apoptosis, cell cycle arrest, andviaantioxidative effects.

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