Inhibitory effects of Hochu-ekki-to on endometrial carcinogenesis induced by N-methyl-N-nitrosourea and 17β-estradiol in mice

Abstract

An evaluation of the effects of a traditional Chinese herbal medicine, Hochu-ekki-to (Bu-zong-yi-qi-tang) on endometrial carcinogenesis was performed in experiments with female mice. In the short-term experiment, dietary exposure of Hochu-ekki-to (0.2% for 2 weeks) decreased the estradiol-17ß (E2)-stimulated expression levels of c-jun (P<0.001), tumor necrosis factor (TNF)-• (P<0.005), estrogen receptors (ER)-• (P<0.001) and ER-ß (P<0.005), as determined by reverse transcription-polymerase chain reaction and a Southern blot analysis in the uteri of the ovarectomized mice. In the long-term experiment, the mice were given N-methyl-N-nitrosourea (MNU) solution (1 mg/100 g body weight) and normal saline (as controls) into their left and right uterine corpora, respectively, and then were divided into four groups. Group 1 (25 mice) was given a diet with Hochu-ekki-to and 5 ppm E2. Group 2 (25 mice) was given a diet with E2 alone. Group 3 (25 mice) was given a diet with Hochu-ekki-to alone. Group 4 (25 mice) was kept on the basal diet alone and treated as a control. The incidence of uterine endometrial cancer in the group with Hochu-ekki-to treatment was substantially lower than of the control group. The inhibitory effect of Hochu-ekki-to on endometrial carcinogenesis is thus suggested to decrease the expressions of c-jun, TNF-•, ER-• and-ß.

Chemopreventative Effect of Hochu-ekki-to (TJ-41) on Chemically Induced Biliary Carcinogenesis in Hamsters

“…We have obtained evidence that persistent cholangitis after bilioenterostomy in hamsters accelerates the development of biliary carcinoma through an increase in the proliferative activity of the biliary epithelium in accordance with the severity of cholangitis (9,10) and that etodolac, a selective COX-2 inhibitor, reduces both the occurrence of severe cholangitis and the acceleration of biliary epithelial cell kinetics after bilioenterostomy in hamsters, resulting in the prevention of BOP-induced biliary carcinogenesis (34). Recently, some studies have proved that TJ-41 reduced the development of several kinds of cancer (17)(18)(19)(20) and activities of inflammatory cytokines (35)(36)(37). …”

“…On the other hand, TJ-41 has recently been reported to activate macrophages and natural killer (NK) cells (13)(14)(15). Moreover, some studies have demonstrated that TJ-41 inhibits experimental liver metastasis (16) and also exerts an anti-neoplastic effect in several kinds of malignant tumors, including skin cancer, hepatoma, ovarian cancer, and uterine cancer (17)(18)(19)(20).…”

A Brief Review on the Experimental Aspects of Bojungikki-Tang in Cancer

“…These data support that BJIKT augmented antitumor immune response in stress-burdened, tumor-bearing mice 23 . Onogi's group performed endometrial carcinogenesis, in ICR mice, induced by N-Methyl-N-Nitrosourea (MNU) into the left uterine tube and normal saline was injected into the opposite side 24 . Diet with 17ß-estradiol (E2) alone, E2 plus BJIKT, was given and incidence of prenoplastic and neoplastic mouse endometrial lesions were measured 24 .…”

“…Onogi's group performed endometrial carcinogenesis, in ICR mice, induced by N-Methyl-N-Nitrosourea (MNU) into the left uterine tube and normal saline was injected into the opposite side 24 . Diet with 17ß-estradiol (E2) alone, E2 plus BJIKT, was given and incidence of prenoplastic and neoplastic mouse endometrial lesions were measured 24 . The incidence of adenocarcinoma was significantly less in BJIKT treated mice 24 .…”

“…Diet with 17ß-estradiol (E2) alone, E2 plus BJIKT, was given and incidence of prenoplastic and neoplastic mouse endometrial lesions were measured 24 . The incidence of adenocarcinoma was significantly less in BJIKT treated mice 24 . In addition, it was suggested that decrease in expression of c-Jun, TNF-α, ER-α and ER -β mediates the inhibitory effect of BJIKT on endometrial carcinogenesis 24 .…”