Biological investigation of the platinum(II)-[*I]iodohistamine complexes of potential synergistic anti-cancer activity.
Cisplatin chemotherapy in combination with external irradiation or with low-dose continuous internal radiotherapy produces significant supra-additive treatment effects towards several tumor cells. The purpose of our research is to develop a new class of platinum-based anticancer drugs containing moieties of synergistic potency such as platinum core and a radiotherapeutic isotope which, delivered directly to the tumorous cells by a specifically designed vectors, should produce a local enhancement of therapeutic dose. Thus, we have synthesized a new platinum-iodohistamine complex and its radioactive analogues labeled with I-125 and I-131. In the present study some biological properties of those compounds have been investigated. The in vitro screening study pointed out that non-radioactive platinum-iodohistamine complex possesses high cytostatic activity against COLO-205 cells, and moderate activity against HL-60 cell line. No cytotoxicity was observed against MOLT-4 and L-1210 cells, as well as against VERO normal cells. The biodistribution of intravenously administered radioactive platinum-[131I]-iodohistamine complex to normal rats revealed the highest accumulation in the liver (c.a. 40%ID). Intraperitoneal injections of the complex to tumor-bearing C3H mice resulted in scattering of the dose in the organs (mainly in GIT, liver, kidney). The retention of radioactive complex in neoplastic tissue was 3-4 times higher than in normal muscular tissue, although exhibited the tendency to decrease with time post injection. The results of the present study show promising features of the newly developed platinum-iodohistamine complexes and justify prospective investigation of in vivo anticancer potency on animal models of solid tumors.
Garnuszek
Piotr
P
Drug Institute, 30/34 Chelmska St., 00-725, Warsaw, Poland. pg@il.waw.pl
Liciańska
Iwona
I
Skierski
Janusz S
JS
Koronkiewicz
Mirosława
M
Mirowski
Marek
M
Wiercioch
Rafał
R
Mazurek
Aleksander P
AP
D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D003110:Colonic Neoplasms / Q000473:pathology / Q000628:therapy; D004357:Drug Synergism; D005260:Female; D005434:Flow Cytometry; D006632:Histamine / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007939:Leukemia L1210 / Q000628:therapy; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000532:radiotherapy; D051379:Mice; D008809:Mice, Inbred C3H; D009944:Organoplatinum Compounds / Q000493:pharmacokinetics / Q000494:pharmacology*; D018714:Radiotherapy, Adjuvant / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured / Q000187:drug effects
C455111:(iodohistamine)platinum(II); D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D006632:Histamine