Cancer chemoprevention agent development strategies for genistein.
Cancer chemoprevention refers to the reduction of cancer incidence by administration of agents or drugs that inhibit, reverse or retard the cancer process. Genistein has demonstrated a wide variety of biological activities that make it a good candidate for a chemopreventive agent. Many agents, such as genistein, are currently being tested with the goal of developing safe and effective chemopreventive drugs for human use. Genistein was investigated as a potential chemopreventive agent in an azoxymethane-induced colon carcinogenesis model. Genistein was tested for its ability to inhibit aberrant colon crypts in the colon of F344 rats that had been treated with azoxymethane. Genistein was administered in the diet from 1 wk before the carcinogen to 4 wk after the first carcinogen dose for a total of 5 wk. At both doses, 75 and 150 mg/kg, the mean number of foci per colon was significantly reduced. Further development of this agent includes demonstration of the preventive efficacy in an in vivo tumorigenesis model, followed by preclinical pharmacology and toxicology testing. Phase 1, 2 and 3 clinical chemoprevention trials would be then performed to determine pharmacokinetics, safe doses, and effectiveness for New Drug Approval.
Steele
V E
VE
Chemoprevention Branch, National Cancer Institute, Bethesda, MD 20892.
Pereira
M A
MA
Sigman
C C
CC
Kelloff
G J
GJ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000592:standards / Q000627:therapeutic use*; D003106:Colon / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000453:epidemiology / Q000517:prevention & control; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D019833:Genistein; D015994:Incidence; D007529:Isoflavones / Q000494:pharmacology / Q000592:standards / Q000627:therapeutic use*; D008297:Male; D008871:Microvilli / Q000187:drug effects / Q000648:ultrastructure; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000453:epidemiology / Q000517:prevention & control*; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
D000970:Antineoplastic Agents; D007529:Isoflavones; D019833:Genistein