[Studies on the anti-tumorpromotion activities of dehydroepiandrosterone and its mechanism of action].
OBJECTIVE
To investigate the anti-tumorpromoting activity of dehydroepiandrosterone (DHEA) and its mechanism of action.


METHODS
Using croton oil-induced ear edema model and applying confocal laser scanning microscopy, flow cytometry, immuno-fluorescent techniques to investigate the inhibitory effect of DHEA on tumor promotion.


RESULTS
DHEA 25 mg.kg-1 was shown to inhibit croton oil induced ear edema in mice by 51%. DHEA at dose of 40 mg.kg-1 and 10 mg.kg-1 exhibited inhibitory effects on croton oil-induced ornithine decarboxylase (ODC) activity by 64% and 53%, respectively. These results revealed that DHEA can block the change of cell cycle and the percentage of S phase was decreased to 17% at concentration of 10(-7) mol.L-1. The increase of[Ca2+]i and pH as well as PKC-activation induced by TPA stimulation were significantly inhibited by DHEA pretreatment.


CONCLUSIONS
The present experiments demonstrate that DHEA appears to be an attractive candidate as an anti-tumorpromotion agent for tumor chemoprevention. The mechanism of its action might be related to its inhibitory effects on ODC activity and Ca(2+)-DG-PKC signal pathway.
Yang
S
S
Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China.
Fu
Z D
ZD
Han
R
R
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002118:Calcium / Q000378:metabolism; D003436:Croton Oil; D003687:Dehydroepiandrosterone / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D004817:Epidermis / Q000201:enzymology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009369:Neoplasms / Q000517:prevention & control; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D016588:Anticarcinogenic Agents; D003687:Dehydroepiandrosterone; D003436:Croton Oil; D011493:Protein Kinase C; D009955:Ornithine Decarboxylase; D002118:Calcium