Abstract |
In the present study, in order to investigate the anticancer effects of O-desmethylangolensin (O-DMA) on human hepatocellular carcinoma Hep3B cells, we first examined the antiproliferative effect of O-DMA. When Hep3B cells were treated with O-DMA at various concentrations (5-200 µM) for 24, 48 or 72 h, cell proliferation decreased significantly in a dose- and time-dependent manner. Moreover, O-DMA exposure at the IC50 concentration for 72 h arrested cells at the G2/M phase, which was accompanied by a reduction in CDK1, and an increase in cyclin A and B. Under the same conditions, O-DMA significantly increased the number of sub-G1 phase cells. Additionally, an Annexin V assay revealed that exposure to O-DMA affected the rate of cell apoptosis. O-DMA caused the downregulation of Bcl-2 and upregulation of Bax, which led to cytochrome c release from the mitochondria and activation of caspase-3. Taken together, these data suggest that O-DMA exhibits anticancer activity by arresting the cell cycle at G2/M phase and causing mitochondrial-dependent apoptosis in Hep3B cells.
|
Authors | Eun Jeong Choi, Jae-In Lee, Gun-Hee Kim |
Journal | International journal of molecular medicine
(Int J Mol Med)
Vol. 31
Issue 3
Pg. 726-30
(Mar 2013)
ISSN: 1791-244X [Electronic] Greece |
PMID | 23314756
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Antineoplastic Agents
- Cyclin A
- Cyclin B
- Isoflavones
- Phytoestrogens
- Proto-Oncogene Proteins c-bcl-2
- Cytochromes c
- CDC2 Protein Kinase
- Caspase 3
- O-desmethylangolensin
|
Topics |
- Antineoplastic Agents
(pharmacology)
- Apoptosis
(drug effects)
- CDC2 Protein Kinase
(biosynthesis)
- Carcinoma, Hepatocellular
(drug therapy)
- Caspase 3
(metabolism)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Cyclin A
(biosynthesis)
- Cyclin B
(biosynthesis)
- Cytochromes c
(metabolism)
- G2 Phase Cell Cycle Checkpoints
(drug effects)
- Humans
- Isoflavones
(pharmacology)
- Liver Neoplasms
(drug therapy)
- Mitochondria
(metabolism)
- Phytoestrogens
(pharmacology)
- Proto-Oncogene Proteins c-bcl-2
(biosynthesis)
|