Anti-tumor-promoting activity of simple models of galactoglycerolipids with branched and unsaturated acyl chains.
Six new galactoglycerolipid analogs, in which one or two 4-methylpentanoyl or trans-2-butenoyl groups are linked to the 2-O-beta-D-galactosylglycerol skeleton, were tested for their anti-tumor-promoting activity using a short-term in vitro assay for Epstein-Barr virus early antigen (EBV-EA) activation. All these compounds were more active than their linear or saturated reference compounds in inhibiting the EBV activation promoted by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), the diester 1-O-(4-methylpentanoyl)-2-O-[6-O-(4-methylpentanoyl)-beta-D-galactopyranosyl]-sn-glycerol resulting the most active glycoglycerolipid analog till now tested. Four compounds (three butenoates and one 4-methylpentanoate), when tested in the in vivo two-stage carcinogenesis test, exhibited also inhibitory effects on mouse skin tumor promotion.
Colombo
Diego
D
Dipartimento di Chimica, Biochimica e Biotecnologie per la Medicina, Università di Milano, Via Saldini 50, 20133 Milano, Italy. diego.colombo@unimi.it
Franchini
Laura
L
Toma
Lucio
L
Ronchetti
Fiamma
F
Nakabe
Nami
N
Konoshima
Takako
T
Nishino
Hoyoku
H
Tokuda
Harukuni
H
D000818:Animals; D000956:Antigens, Viral / Q000187:drug effects; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D038983:Galactolipids / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D018716:Molecular Mimicry; D010212:Papilloma / Q000188:drug therapy / Q000473:pathology; D012878:Skin Neoplasms / Q000188:drug therapy / Q000473:pathology; D013329:Structure-Activity Relationship; D047368:Tumor Burden / Q000187:drug effects*
D000956:Antigens, Viral; D000970:Antineoplastic Agents; C033305:Epstein-Barr virus early antigen; D038983:Galactolipids