Preventive effect of Juzen-taiho-to on endometrial carcinogenesis in mice is based on Shimotsu-to constituent.
Juzen-taiho-to, a Kampo formula, originally consists of a mixture of Shimotsu-to and Shikunshi-to formulas together with two other crude ingredients. Juzen-taiho-to is reported to have a preventive effect on endometrial carcinogenesis in mice. Shimotsu-to exerts an inhibitory effect on estrogen-induced expression of c-fos, interleukin (IL)-1alpha and tumor necrosis factor (TNF)-alpha in uteri of ovarectomized mice. In the present study, short- and long-term experiments were designed to determine the effects of Juzen-taiho-to and Shimotsu-to on the estrogen-related endometrial carcinogenesis in mouse uteri, associated with the expression of cyclooxygenase (COX)-1 and -2. In the short-term experiment, exposure to Juzen-taiho-to or Shimotsu-to significantly reduced estradiol-17beta (E(2))-stimulated expressions of COX-2 mRNA (p<0.05) as well as the protein. However, no effects on the expression of COX-1 were observed. Shikunshi-to did not affect COX expression. In the long-term experiment, 90 female ICR mice were given N-methyl-N-nitrosourea (MNU) into their uterine corpora. The animals were divided into four groups as follows: group 1, a diet containing 0.07% Shimotsu-to and 5 ppm E(2); group 2, a diet containing 5 ppm E(2); group 3, a diet containing 0.07% Shimotsu-to; group 4 served as a control. Exposure of Shimotsu-to reduced the incidence of MNU- and E(2)-induced endometrial adenocarcinoma and atypical hyperplasia at the termination of the experiment (30 weeks). The above findings and our previous reports suggest that Shimotsu-to is responsible for the preventive effects of Juzen-taiho-to on estrogen-related endometrial carcinogenesis in mice, through the inhibition of estrogen-related COX-2 as well as c-fos, IL-1alpha and TNF-alpha expressions.
Tagami
Keiko
K
Department of Obstetrics and Gynecology, Gifu University School of Medicine, 40 Tsukasa-machi, Gifu 500-8705, Japan.
Niwa
Kenji
K
Lian
Zenglin
Z
Gao
Jingchun
J
Mori
Hideki
H
Tamaya
Teruhiko
T
D000818:Animals; D016588:Anticarcinogenic Agents / Q000737:chemistry / Q000494:pharmacology*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D016889:Endometrial Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D004958:Estradiol; D005260:Female; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D020835:Medicine, Kampo; D008565:Membrane Proteins; D008770:Methylnitrosourea; D051379:Mice; D008813:Mice, Inbred ICR; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016588:Anticarcinogenic Agents; D004365:Drugs, Chinese Herbal; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; C493685:Shikunshi-to; C063587:juzentaihoto; C079710:shimotsu-to; D004958:Estradiol; D008770:Methylnitrosourea; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse