In vitro cytostatic activity and DNA-interaction of the new liver organotropic complex chloro-bis-cholylglycinate-platinum (II).
BACKGROUND
The liver organotropic properties of the new bioinorganic complex of platinum (II) and glycocholic acid, Bamet-H2 have been reported previously. The aim of this work was to investigate the in vitro cytostatic activity of this compound.


METHODS
The inhibition of cell growth and DNA synthesis by mouse leukemia L-1210 (mL), mouse hepatoma Hepa 1-6 (mH), rat hepatoma McA-RH7777 (rH) and human colon adenocarcinoma LS-174T (hCC) cells were measured. The effects on the electrophoretic mobility of the pUC18 plasmid, the DNA denaturation temperature and ethidium bromide (EthBr) binding to DNA were studied.


RESULTS
A significant antiproliferative effect for Bamet-H2 was found (mH approximately hCC > mL approximately rH). DNA synthesis was also markedly inhibited (mH approximately hCC approximately mL approximately rH). Bamet-H2-induced a change in the electrophoretic mobility of pUC18 and the increase in DNA denaturation temperature suggested the existence of DNA-Bamet-H2 interactions. Scatchard plots obtained from EthBr displacement assays revealed that Bamet-H2 induces a reduction in both the number of DNA sites available and their ability to bind EthBr.


CONCLUSIONS
Bamet H2 is able to interact with DNA, inhibit DNA synthesis, and hence reduce cell proliferation.
Department of Physiology and Pharmacology, University of Salamanca, Spain. jjgmarin@gugu.usal.es
J J
JJ
Marin
M F
MF
Palomero
M C
MC
Herrera
R I
RI
Macias
J J
JJ
Criado
M A
MA
Serrano
D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003110:Colonic Neoplasms / Q000473:pathology*; D004261:DNA Replication / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D004996:Ethidium / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D007939:Leukemia L1210 / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000473:pathology*; D051379:Mice; D009691:Nucleic Acid Denaturation; D009942:Organometallic Compounds / Q000633:toxicity*; D051381:Rats; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D009942:Organometallic Compounds; C112413:bamet H2; D004996:Ethidium