Preventive effects of glycyrrhizin on estrogen-related endometrial carcinogenesis in mice

Abstract

Abstract. We have previously reported on the inhibitory effect of Glycyrrhizae radix (Gl radix) on mouse endometrial carcinogenesis. The present study was performed to clarify the effects of Gl radix and glycyrrhizin (GL), the main part of Gl radix, on estradiol (E 2 )-related endometrial carcinogenesis. Both Gl radix and GL exerted a significant decrease in the COX-2, IL-1· and TNF-· mRNA expressions. GL generated a significant decrease in the incidence of endometrial adenocarcinoma. Accordingly, the preventive effects of Gl radix may be attributable to GL, thus being related with the suppression of COX-2, IL-1· and TNF-·. Gl radix and GL could therefore be a promising formula for the chemoprevention of human endometrial cancer. IntroductionGlycyrrhizin (GL), a major constituent of Glycyrrhizae radix (Gl radix) which is ~10% of the dry weight of Gl radix extract, is the calcium and potassium salt of glycyrrhizinic acid. GL glycoside loses its sweet taste and upon hydrolysis is then converted to aglycone glycyrrhetinic acid plus two molecules of glucuronic acid. GL has an anti-estrogenic as well as an estrogenic effect (1). There is some evidence that GL has a protective effect on the skin (2,3) or liver carcinogenesis (4,5).It is known that Gl radix is widely used as a Kampo medicine in Asian countries and ~75% of traditional Japanese and Chinese medicines contain this agent. We have previously reported that Gl radix has a preventive effect on endometrial carcinogenesis in mice, and this effect is related to the inhibition of the expression of estrogen-stimulated genes c-fos/jun mRNA and proteins (6). We also proved that the herbal complex containing Gl radix suppresses cell proliferation in a chemo-endocrine resistant cancer cell line (7). In general, the anti-estrogenic effects are considered to have a protective effect against the occurrence of estrogendependent cancers. Such effects are confirmed in animal models of uterine endometrial cancer (8).Cyclooxygenase (COX), an enzyme that activates the production of prostaglandins from arachidonic acid, has two isoforms. COX-2 has attracted considerable attention in connextion with carcinogenesis in organs such as the large bowel, mammary glands and breast carcinogenesis (9-11). There is evidence that the COX activity is related to the promotion and progression in the tumorigenesis of the prostatic gland, stomach and lung (12)(13)(14). It remains unclear whether COX-2 is involved in E 2 related mouse endometrial carcinogenesis, although a high expression level of COX-2 has been confirmed in human endometrial carcinomas (15). In this study, we examined the possible association of the preventive effects of GL on E 2 -induced mouse endometrial carcinogenesis with COX-2 activity.We have reported that the expression of internal cytokines, interleukin (IL)-1· and tumor necrosis factor (TNF)-·, increase after E 2 treatment (16). Such an increase of the internal cytokines is suggested to contribute to both tumor promotion and progression (17)(18)(19). Such circumstances ...

Chemopreventive Effects of Licorice and Its Components

“…Researchers have also shown that Gc or GA reduced melanoma cell proliferation [31] and metastasis [32]. Other cancers that have been reported to be sensitive to the antiproliferative effects of GA or Gc include UVB-induced skin carcinogenesis [33•], prostate cancer [34], stomach cancer and leukemia [35,36], gastric cancer [37], endometrial carcinogenesis [38], pituitary adenomas [39], and breast cancer [40]. GA was reported to suppress A549 and NCI-H460 non-small cell lung cancer (NSCLC) growth and inhibit thromboxane synthase activity [41].…”

18α-glycyrrhetinic acid targets prostate cancer cells by down-regulating inflammation-related genes

“…The major active component of licorice root is glycyrrhizin, an oleanane-type triterpene saponin which constitutes 2-24% of total dry weight (7). Glycyrrhizin is extensively reported to have several pharmacological activities including anti-inflammatory (8), immunomodulatory (9), antiulcer (10) and anti-tumorigenic activities (11,12). Glycyrrhizin also has antiviral activity against hepatitis B virus, HIV (13,14) and severe acute respiratory syndrome (SARS)-associated coronavirus (15).…”

Fetal and Neonatal Outcomes in Women Reporting Ingestion of Licorice (Glycyrrhiza uralensis) during Pregnancy

“…In mice, administration of licorice extracts had anti-nephritic properties [13,14], which were linked to its free radical scavenging properties. Furthermore, licorice may suppress estrogen-induced c-fos/jun expressions and decrease the incidences of uterine endometrial atypical hyperplastic and malignant lesions in mice [15]. However, there is no mechanistic support for most of the other effects claimed for licorice.…”