title: Antitumor properties of diastereomeric and geometric analogs of vitamin D3.
abstract: Analogs of 1,25-dihydroxyvitamin D3 with a reversed configuration at C-1 or C-24 and E or Z geometry of the double bond at C-22 in the side chain or at C-5 in the triene system were examined for their antiproliferative activity in vitro against a spectrum of various human cancer cell lines. The analogs coded PRI-2201 (calcipotriol), PRI-2202 and PRI-2205, such as calcitriol and tacalcitol (used as a referential agents), revealed antiproliferative activity against human HL-60, HL-60/MX2, MCF-7, T47D, SCC-25 and mouse WEHI-3 cancer cell lines. The toxicity studies in vivo showed that PRI-2202 and PRI-2205 are less toxic than referential agents. Even at total doses of 2.5-5.0 mg/kg distributed during 5 successive days, no changes in body weight were observed. Calcitriol and tacalcitol showed toxicity in the same protocol at 100 times lower doses. Calcipotriol was lethal to all mice after administration of a total dose of 5.0 mg/kg. The analog PRI-2205 appeared to be more active in mouse Levis lung cancer tumor growth inhibition than calcitriol, calcipotriol or PRI-2202. This analog did not reveal calcemic activity at doses which inhibit tumor growth in vivo nor at higher doses.
authors.affiliation: Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław bPharmaceutical Research Institute, Warsaw, Poland. wietrzyk@iitd.pan.wroc.pl
authors.forename: Joanna
authors.initials: J
authors.lastname: Wietrzyk
authors.forename: Michał
authors.initials: M
authors.lastname: Chodyński
authors.forename: Hanna
authors.initials: H
authors.lastname: Fitak
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Wojdat
authors.forename: Andrzej
authors.initials: A
authors.lastname: Kutner
authors.forename: Adam
authors.initials: A
authors.lastname: Opolski
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D039481:CD11b Antigen / Q000378:metabolism; D002117:Calcitriol / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000097:blood; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002762:Cholecalciferol / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000633:toxicity; D004396:Coloring Agents; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology; D012235:Rhodamines; D013237:Stereoisomerism; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D000970:Antineoplastic Agents; D039481:CD11b Antigen; D004396:Coloring Agents; D018950:Lipopolysaccharide Receptors; D012235:Rhodamines; D013778:Tetrazolium Salts; D013844:Thiazoles; C055085:calcipotriene; D002762:Cholecalciferol; C022027:lissamine rhodamine B; C022616:thiazolyl blue; D002117:Calcitriol; D002118:Calcium