LA-12 overcomes confluence-dependent resistance of HT-29 colon cancer cells to Pt (II) compounds.
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.


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.


CONCLUSIONS
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.
Department of Cytokinetics, Institute of Biophysics, Academy of Sciences of the Czech Republic, Královopolská 135, 612 65 Brno, Czech Republic.
Lenka
L
Svihálková-Sindlerová
Vendula
V
Foltinová
Alena
A
Vaculová
Viktor
V
Horváth
Karel
K
Soucek
Petr
P
Sova
Jirina
J
Hofmanová
Alois
A
Kozubík
D000230:Adenocarcinoma / Q000188:drug therapy*; D000547:Amantadine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D019073:HT29 Cells; D006801:Humans; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C482801:bis(acetato)(1-adamantylamine)amminedichloroplatinum(IV); D000077150:Oxaliplatin; D000547:Amantadine; D002945:Cisplatin