Modulation of in vitro biomarkers of the carcinogenic process by chemopreventive agents.
A structurally diverse group of chemopreventive agents was evaluated using in vitro biomarkers of the carcinogenesis process. With cultured human bronchial epithelial (BEAS-2B) cells, sulfur-containing compounds such as 1.2-dithiole-3-thione and sulforaphane, and phenolic compounds such as caffeic acid phenethyl ester and genistein, showed potent inhibition of benzo(a)pyrene [B(a)P] metabolite-DNA binding. Phenolic compounds also demonstrated strong antioxidant activity. Most of the test compounds did not inhibit 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ornithine decarboxylase (ODC) activity with cultured mouse epidermal ME 308 cells, with the exception of sulfur-containing compounds, 1,2-dithiole-3-thione and sulforaphane, and a selenium compound, 1,4-phenylenebis (methylene)selenocyanate. With cultured Hepa 1c1c7 cells, sulforaphane and 1,2-dithiole-3-thione mediated strong induction of quinone reductase, and genistein and ursolic acid were moderate inducers. Chalcone, 1,4-phenylenebis (methylene)selenocyanate and caffeic acid phenethyl ester induced HL-60 cell differentiation. Interestingly, sulforaphane and caffeic acid phenethyl ester inhibited the total metabolism of benzo(a)pyrene with cultured BEAS-2B cells, and the distribution pattern of water-soluble metabolites was altered in comparison with the control groups. These data are suggestive of pleiotropic mechanisms that should prove beneficial when considering the chemopreventive activity of these substances. As a result, of the group of 25 agents tested, four were judged as superior cancer chemopreventive agents: caffeic acid phenethyl ester, 1,2-dithiole-3-thione, genistein, and sulforaphane.
Lee
S K
SK
Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago 60612, USA.
Song
L
L
Mata-Greenwood
E
E
Kelloff
G J
GJ
Steele
V E
VE
Pezzuto
J M
JM
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001564:Benzo(a)pyrene / Q000378:metabolism; D015415:Biomarkers; D002454:Cell Differentiation / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D005982:Glutathione Transferase / Q000096:biosynthesis; D018922:HL-60 Cells / Q000187:drug effects; D006801:Humans; D051379:Mice; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000096:biosynthesis; D065108:Ornithine Decarboxylase Inhibitors
D016588:Anticarcinogenic Agents; D015415:Biomarkers; D065108:Ornithine Decarboxylase Inhibitors; D001564:Benzo(a)pyrene; D004247:DNA; D016660:NAD(P)H Dehydrogenase (Quinone); D005982:Glutathione Transferase