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LA-12 overcomes confluence-dependent resistance of HT-29 colon cancer cells to Pt (II) compounds
L. Švihálková-Šindlerová, V. Foltinová, A. Vaculová, V. Horváth, K. Souček, P. Sova, J. Hofmanová, A. Kozubík
Language English Country Greece
Document type Journal Article, Research Support, Non-U.S. Gov't
NLK
Free Medical Journals
from 2004 to 2 years ago
Open Access Digital Library
from 2004-01-01
PubMed
20530425
Knihovny.cz E-resources
- MeSH
- Adenocarcinoma drug therapy MeSH
- Amantadine analogs & derivatives pharmacology MeSH
- Apoptosis drug effects MeSH
- Cell Adhesion drug effects MeSH
- HT29 Cells MeSH
- Drug Resistance, Neoplasm MeSH
- Cisplatin pharmacology MeSH
- Humans MeSH
- Colonic Neoplasms drug therapy pathology MeSH
- Organoplatinum Compounds pharmacology MeSH
- Antineoplastic Agents pharmacology MeSH
- Dose-Response Relationship, Drug MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
BACKGROUND: LA-12 is a new platinum (IV) drug with promising cytotoxic effects in a wide range of cancer cell lines. Its confluence-dependent effects were compared with cisplatin (CDDP) and oxaliplatin (L-OHP) in HT-29 cells. MATERIALS AND METHODS: Cytotoxicity was determined by MTT test, eosin exclusion assay, and cell number quantification. The cell cycle was analysed using propidium iodide DNA staining (flow cytometry), apoptosis by phosphatidylserine externalisation (annexin-V assay), mitochondrial membrane potential by flow cytometry, nuclear morphology by means of fluorescence microscopy, and PARP cleavage by Western blotting. RESULTS: While L-OHP and CDDP were practically inactive in the subconfluent cell population, LA-12 showed a similar toxicity in both subconfluent and growing populations. All compounds induced apoptosis, although with different potentials. CONCLUSION: LA-12 was able to overcome confluence-dependent resistance of HT-29 cells observed for other platinum compounds, which may have potential therapeutic use in slowly growing tumours.
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- $a Švihálková Šindlerová, Lenka $7 xx0121174 $u Department of Cytokinetics, Institute of Biophysics, Academy of Sciences of the Czech Republic, Královopolská 135, 612 65 Brno, Czech Republic.
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- $a BACKGROUND: LA-12 is a new platinum (IV) drug with promising cytotoxic effects in a wide range of cancer cell lines. Its confluence-dependent effects were compared with cisplatin (CDDP) and oxaliplatin (L-OHP) in HT-29 cells. MATERIALS AND METHODS: Cytotoxicity was determined by MTT test, eosin exclusion assay, and cell number quantification. The cell cycle was analysed using propidium iodide DNA staining (flow cytometry), apoptosis by phosphatidylserine externalisation (annexin-V assay), mitochondrial membrane potential by flow cytometry, nuclear morphology by means of fluorescence microscopy, and PARP cleavage by Western blotting. RESULTS: While L-OHP and CDDP were practically inactive in the subconfluent cell population, LA-12 showed a similar toxicity in both subconfluent and growing populations. All compounds induced apoptosis, although with different potentials. CONCLUSION: LA-12 was able to overcome confluence-dependent resistance of HT-29 cells observed for other platinum compounds, which may have potential therapeutic use in slowly growing tumours.
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