Cancer chemopreventive activities of S-3-1, a synthetic derivative of danshinone.
Salvia miltiorrhiza is a traditional Chinese medicine which has been well documented for its anti-cancer effects. Based on the structure of danshinone, one of the active compounds derived from Salvia miltiorrhiza, we synthesized a simplified phenolic analog, S-3-1, and tried to explore its possible actions in preventing the development of cancer. With the Ames test, S-3-1 was found to efficiently suppress the mutagenicity of benzo[alpha]pyrene. This result is consistent with the inhibitory effect of S-3-1 on the activation of benzo[alpha]pyrene by hepatic microsomal enzymes. Besides the anti-initiation effects, S-3-1 could significantly inhibit the croton oil-induced increase of mouse skin epithermal ornithine decarboxylase activity. Moreover, S-3-1 quenched both superoxide and hydroxyl free radicals whereas it inhibited lipid peroxidation in the in vitro model. These results suggest that S-3-1 might act as anti-initiation and anti-promotion agents through reversing the biochemical alterations induced by carcinogen during carcinogenesis. Therefore, we further investigated the effects of S-3-1 on carcinogenesis. In vitro, S-3-1 inhibited the benzo[alpha]pyrene-induced transformation of V79 Chinese hamster lung fibroblasts. At 10-40 mg/kg, S-3-1 was found to inhibit the development of DMBA/croton oil-induced skin papilloma in mice through decreasing the incidence of papilloma, prolonging the latent period of tumor occurrence and reducing tumor number per mouse in a dose-dependent manner. We concluded from this study that S-3-1 might be developed as a new chemopreventive drug.
Chen
X G
XG
Department of Pharmacology, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing. chxg@imm.ac.cn
Li
Y
Y
Yan
C H
CH
Li
L N
LN
Han
R
R
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D016588:Anticarcinogenic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000493:pharmacokinetics / Q000494:pharmacology*; D001564:Benzo(a)pyrene; D001572:Benzofurans / Q000737:chemistry / Q000302:isolation & purification* / Q000493:pharmacokinetics / Q000494:pharmacology*; D015764:Bepridil / Q000031:analogs & derivatives* / Q000633:toxicity; D001713:Biphenyl Compounds; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced; D002478:Cells, Cultured / Q000187:drug effects; D006224:Cricetinae; D003436:Croton Oil; D003545:Cysteine / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000737:chemistry*; D004847:Epithelial Cells / Q000201:enzymology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D016166:Free Radical Scavengers / Q000737:chemistry / Q000302:isolation & purification* / Q000493:pharmacokinetics / Q000494:pharmacology*; D019271:Hypoxanthine / Q000633:toxicity; D066298:In Vitro Techniques; D007501:Iron / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008516:Medicine, Chinese Traditional; D051379:Mice; D008813:Mice, Inbred ICR; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D015394:Molecular Structure; D009153:Mutagens; D009952:Ornithine / Q000378:metabolism; D009955:Ornithine Decarboxylase / Q000378:metabolism; D010212:Papilloma / Q000139:chemically induced*; D004369:Pentetic Acid / Q000633:toxicity; D010616:Phenanthrenes / Q000737:chemistry / Q000302:isolation & purification* / Q000493:pharmacokinetics / Q000494:pharmacology*; D010851:Picrates; D010946:Plants, Medicinal / Q000737:chemistry*; D051381:Rats; D012475:Salmonella / Q000187:drug effects; D012867:Skin / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D012878:Skin Neoplasms / Q000139:chemically induced*; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship; D014969:Xanthine Oxidase / Q000378:metabolism
D016588:Anticarcinogenic Agents; D001572:Benzofurans; D001713:Biphenyl Compounds; D004365:Drugs, Chinese Herbal; D016166:Free Radical Scavengers; D009153:Mutagens; D010616:Phenanthrenes; D010851:Picrates; C435020:S-3-1 compound; C435019:danshinone; D019271:Hypoxanthine; D001564:Benzo(a)pyrene; D015127:9,10-Dimethyl-1,2-benzanthracene; D015764:Bepridil; D004369:Pentetic Acid; D003436:Croton Oil; C004931:1,1-diphenyl-2-picrylhydrazyl; D007501:Iron; D009952:Ornithine; D014969:Xanthine Oxidase; D009955:Ornithine Decarboxylase; D003545:Cysteine