Antitumor effect of 22-oxa-1 alpha,25-dihydroxyvitamin D3, a potent angiogenesis inhibitor, on rat mammary tumors induced by 7,12-dimethylbenz[a]anthracene.
The effect of 22-oxa-1 alpha,25-dihydroxyvitamin D3 (22-oxa-1,25(OH)2D3) on the growth of autochthonous rat mammary tumors induced by 7,12-dimethylbenz[a]anthracene (DMBA) was examined on the basis of our previous finding that this synthetic vitamin D3 analog has a potent angiogenesis inhibitory effect. Two doses of 22-oxa-1,25(OH)2D3, 0.1 and 1 microgram/kg of body weight, due to the limited amount of the compound available, were used. The daily administration of 22-oxa-1,25(OH)2D3 at the dose of 1 microgram/kg/day resulted in significant inhibition of the growth of these mammary tumors at 1, 2 and 3 weeks after the administration of this agent, although the agent caused little or no regression of the tumors. After daily administration for 3 weeks, a significant antitumor effect was also observed in the group treated with 0.1 microgram/kg/day. Treatment with 22-oxa-1,25(OH)2D3 did not affect the serum calcium levels in the treated rats. The lower dose of 22-oxa-1,25(OH)2D3 neither affected weight gain nor caused a decrease in body weight, while the higher dose, although having some effect on weight gain, did not induce a decrease in body weight. There were no significant differences in the weights of adrenals, uteri and ovaries between the treated groups and controls. These results suggest that 22-oxa-1,25(OH)2D3 has a significant growth inhibitory effect on DMBA-induced autochthonous mammary tumors in rats, without producing severe side effects, including hypercalcemic activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Oikawa
T
T
Division of Cancer Therapeutics, Tokyo Metropolitan Institute of Medical Science, Japan.
Yoshida
Y
Y
Shimamura
M
M
Ashino-Fuse
H
H
Iwaguchi
T
T
Tominaga
T
T
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology; D002118:Calcium / Q000097:blood; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D000970:Antineoplastic Agents; D015127:9,10-Dimethyl-1,2-benzanthracene; D002117:Calcitriol; C051883:maxacalcitol; D002118:Calcium