Modifying effect of organocobalt complexes on the tumour response to anticancer treatments.
A new type of agents are proposed for combined cancer therapy. They are organocobalt (III) chelates containing a sigma-bounded organyl group and a mixed tridentate ligand derived from a Schiff base. These complexes generate free radicals due to the action of protons in physiological ranges of pH and temperature, and hence are conceivably capable of selectively attacking a malignant neoplasm that is slightly acidic and can be made even more so by introducing some means intensifying glycolysis. An in vivo examination was performed using transplanted rat tumours (Guerin and Walker 256 carcinomas, Sarcoma 45). The modifying effect of one of these complexes on the tumour response to cis-DDP, radiation and/or local hyperthermia was tested by means of tumour growth delay assay and local tumour control. The potentiating effect of the complex was maximal when it was administered 60-90 minutes prior to other agents (cisDDP, X-irradiation heat). The enhancement ratio was found to be ca. 2.0-4.0 for cisDDP and 2.0 for radiation. In conclusion, in our tumour models, an increase of the antitumour effect was obtained for conventional antitumour agents when they were supplemented with organocobalt complex. It can be hypothesised that DNA in tumour cells may be considered to be the main target for organocobalt complexes.
Osinsky
S P
SP
Institute Exp. Pathol. Oncol. Radiobiol., Natl. Acad. Sciences of the Ukraine, Kiev, The Ukraine. roman@iepor.kiev.ua
Levitin
I Y
IY
Bubnovskaya
L N
LN
Ganusevich
I I
II
Tsikalova
M V
MV
Istomin
Y P
YP
Zhavrid
E A
EA
Volpin
M E
ME
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols; D003035:Cobalt; D004249:DNA Damage; D005260:Female; D005609:Free Radicals; D006863:Hydrogen-Ion Concentration; D006979:Hyperthermia, Induced; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000628:therapy*; D009942:Organometallic Compounds / Q000008:administration & dosage*; D051381:Rats
D005609:Free Radicals; D009942:Organometallic Compounds; D003035:Cobalt