Source:http://linkedlifedata.com/resource/pubmed/id/16096430
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
8
|
| pubmed:dateCreated |
2005-8-12
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| pubmed:abstractText |
Protein phosphatase 2A (PP2A) is a new target for platinum (Pt)-based cancer chemotherapeutic agents. A series of novel Pt complexes containing demethylcantharidin, a modified component of a traditional Chinese medicine (TCM), [Pt(C8H8O5)(NH2R)2] 1-5 have been shown to inhibit PP2A both in its purified form and in cell homogenates. In this study, the potential efficacy of compounds 1-5 in suppressing the growth of PP2A-highly expressed liver cancer was evaluated. The in vitro anti-proliferative activity of compounds 1-5 was investigated in human hepatocellular carcinoma (HCC) cell lines using the MTT assay. Compounds 1-5 were about 2-20 and 20-200 times more potent than cisplatin and carboplatin, respectively, in SK-Hep1 and HepG2 cells. The in vivo anti-tumor efficacies of 1-5 were evaluated in a s.c. inoculated SK-Hep1 xenograft model in nude mice. Compounds 1-5 demonstrated definite in vivo activity (giving rise to an optimal %T/C as low as 14.5%) without inducing undue toxicity, contrasting the lack of activity of cisplatin and carboplatin. In a cisplatin-resistant model established in vivo in human HCC, compounds 1-5 could still elicit the same level of tumor growth suppression as in the control tumors, demonstrating the circumvention of cisplatin cross-resistance. An acute toxicity study in ICR mice showed that compounds 1-5 are not nephrotoxic at LD10. The high potency of the novel TCM-Pt compounds against liver cancer and the minimal toxicity suggest that they have significant potential to be developed into useful Pt-based anti-tumor drugs.
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| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, Phytogenic,
http://linkedlifedata.com/resource/pubmed/chemical/Carboplatin,
http://linkedlifedata.com/resource/pubmed/chemical/Cisplatin,
http://linkedlifedata.com/resource/pubmed/chemical/Organoplatinum Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoprotein Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Phosphatase 2
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| pubmed:status |
MEDLINE
|
| pubmed:month |
Sep
|
| pubmed:issn |
0959-4973
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
16
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
825-35
|
| pubmed:dateRevised |
2007-11-15
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| pubmed:meshHeading |
pubmed-meshheading:16096430-Animals,
pubmed-meshheading:16096430-Antineoplastic Agents, Phytogenic,
pubmed-meshheading:16096430-Carboplatin,
pubmed-meshheading:16096430-Carcinoma, Hepatocellular,
pubmed-meshheading:16096430-Cisplatin,
pubmed-meshheading:16096430-Drug Resistance, Neoplasm,
pubmed-meshheading:16096430-Humans,
pubmed-meshheading:16096430-Liver Neoplasms, Experimental,
pubmed-meshheading:16096430-Male,
pubmed-meshheading:16096430-Medicine, Chinese Traditional,
pubmed-meshheading:16096430-Mice,
pubmed-meshheading:16096430-Mice, Inbred ICR,
pubmed-meshheading:16096430-Mice, Nude,
pubmed-meshheading:16096430-Organoplatinum Compounds,
pubmed-meshheading:16096430-Phosphoprotein Phosphatases,
pubmed-meshheading:16096430-Protein Phosphatase 2,
pubmed-meshheading:16096430-Structure-Activity Relationship,
pubmed-meshheading:16096430-Time Factors,
pubmed-meshheading:16096430-Tumor Cells, Cultured
|
| pubmed:year |
2005
|
| pubmed:articleTitle |
In vitro and in vivo suppression of growth of hepatocellular carcinoma cells by novel traditional Chinese medicine-platinum anti-cancer agents.
|
| pubmed:affiliation |
School of Pharmacy, Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR.
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| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
|