Source:http://linkedlifedata.com/resource/pubmed/id/18279897
Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
11-12
|
| pubmed:dateCreated |
2008-2-29
|
| pubmed:abstractText |
Studies with Centchroman (CC) as a candidate anti-breast cancer agent are into phase III multicentric clinical trial in stage III/IV breast cancer. We have previously demonstrated its anti-neoplastic activity in Estrogen Receptor positive (ER+ve) MCF-7 Human Breast Cancer Cells (HBCCs). We now present the basis for anti-neoplastic activity of CC, mediated through apoptosis in both ER+ve/-ve MCF-7 and MDA MB-231 HBCCs respectively, compared to Tamoxifen (TAM) as a positive control. All the experiments were performed with 48 h estrogen-deprived cells exposed to CC/TAM for the subsequent 48 h. Cytotoxic potential of CC was assessed through SRB assay. Cell-cycle analysis, Time-dependent cytotoxicity, Reactive Oxygen Species (ROS) and Mitochondrial Membrane Permeability were investigated by Flow Cytometry. Early-stage apoptosis was detected by Annexin-PI staining. Caspases were assayed colorimetrically whereas nuclear derangements were assessed morphologically through PI staining and finally by DNA fragmentation analysis. Cell viability studies confirmed the IC50 of CC in MCF-7 and MDA MB-231 cells to be 10 and 20 microM (P < 0.001) respectively, suggesting enhanced susceptibility of the former cell type to CC. FACS data reveals CC mediated G0/G1 arrest (P < 0.01) along with the presence of prominent sub-G0/G1 peak (P < 0.001) in both the cell types suggesting ongoing apoptosis. Phosphatidylserine externalization, mitochondrial events, caspase evaluation and nuclear morphology changes reveal initiation/progression of caspase-dependent apoptosis even at a dose of 1 microM which eventually leads to DNA fragmentation in both the cell types. Results demonstrate that CC induces caspase-dependent apoptosis in MCF-7 and MDA MB-231 cells irrespective of ER status similar to TAM in terms of anti-neoplastic activity.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Centchroman,
http://linkedlifedata.com/resource/pubmed/chemical/Estrogen Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Tamoxifen
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Mar
|
| pubmed:issn |
0024-3205
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
12
|
| pubmed:volume |
82
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
577-90
|
| pubmed:meshHeading |
pubmed-meshheading:18279897-Antineoplastic Agents,
pubmed-meshheading:18279897-Apoptosis,
pubmed-meshheading:18279897-Breast Neoplasms,
pubmed-meshheading:18279897-Caspases,
pubmed-meshheading:18279897-Cell Line, Tumor,
pubmed-meshheading:18279897-Cell Nucleus,
pubmed-meshheading:18279897-Cell Shape,
pubmed-meshheading:18279897-Cell Survival,
pubmed-meshheading:18279897-Centchroman,
pubmed-meshheading:18279897-Clinical Trials as Topic,
pubmed-meshheading:18279897-DNA Fragmentation,
pubmed-meshheading:18279897-Estrogen Antagonists,
pubmed-meshheading:18279897-Female,
pubmed-meshheading:18279897-G0 Phase,
pubmed-meshheading:18279897-G1 Phase,
pubmed-meshheading:18279897-Humans,
pubmed-meshheading:18279897-Membrane Potentials,
pubmed-meshheading:18279897-Mitochondria,
pubmed-meshheading:18279897-Tamoxifen
|
| pubmed:year |
2008
|
| pubmed:articleTitle |
Centchroman induces G0/G1 arrest and caspase-dependent apoptosis involving mitochondrial membrane depolarization in MCF-7 and MDA MB-231 human breast cancer cells.
|
| pubmed:affiliation |
Tissue and Cell Culture Unit (TCCU), Central Drug Research Institute, Lucknow, 226001, India. manisha992001@yahoo.com
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|