Estrogenic activities of two synthetic pyrethroids and their metabolites

Synthetic pyrethroids （SPs） are among the most common pesticides in current use, and so far, several SPs have been assessed for their potential estrogenicities by various methods. Previous studies have shown that the estrogenicities partly come from their metabolites. Although considerable information is available with respect to the metabolism and environmental degradation of SPs, little is known about the estrogenicities of the metabolites. In this study, permethrin （PM） and β-cypermethrin （CP）, as well as their metabolites （3-phenoxybenzoic alcohol （PBCOH）, 3-phenoxybenzaldehyde （PBCHO） and 3-phenoxybenzoic acid （PBCOOH） were evaluated for their estrogenic activities in the MCF-7 human breast carcinoma cell line. In the MCF-7 cell proliferation assay, PM and CP exhibited significant estrogenic activities at 10-7 mol/L, comparable to 17β-estradiol （E2） of 10-9 tool/L, with the relative proliferative effect ratios of 55.4% and 56.3%, respectively. The real-time quantitative polymerase chain reaction （qRT-PCR） results confirmed the estrogenicities of PM and CP with significant alteration of pS2 and ERα mRNA levels observed at 10-6 mol/L. For the three major metabolites, PBCOH and PBCOOH exhibited estrogenic activities in all assays, while no significant estrogenic responses was observed for PBCHO compared to the vehicle control. In particular, PBCOH had even slightly stronger estrogenic activity than its parent compounds, indicating that metabolism may be one of the reasons for the estrogenicities of the SPs. Given the widespread use of SPs, the toxicological effects of parent compounds and their metabolites should be taken into consideration in the risk assessment of SPs.

Transcriptional activation of Nlp by estrogen-ERa in breast cancer

Estrogen Receptor-a （ERa） is the key transcription factor that regulates cell proliferation and homeosta- sis. In this pathway, estrogen plays an important role in genomic instability and cell cycle regulation pro- cesses and the mechanisms of its action are multifaceted. In this study, we showed that estrogen regulates genomic instability through promoting the expression of Nip, a BRCAl-associated centrosomal protein which is involved in microtubule nucleation, spindle formation, chromosomal missegregation and abnormal cytokinesis. We demonstrated that the expression of Nip is strongly associated with ERa and FOXAI level in clinical breast cancer samples with poor clinical outcomes to breast cancer patients. Addition of estrogen in the ER-positive breast cancer cells resulted in elevation of NLP mRNA. Significantly, we identified that estrogen-ERa is capable of regulating Nlp expression through specifically binding ERa to the proximal region and the Estrogen Responsive Elements （ERE） enhancer in the distal region of NLP gene. Reporter assays demonstrated that estrogen directly activated Nlp promoter. ChIP assay results showed that E2-ERa directly bound to the EREs of Nip. Therefore, overexpression of Nip in breast cancer exhibits a hormone-dependent pattern, and estrogen participates in the regulation of genome instability and cell cycle in breast cancer cells partially through transcriptional activation of NLP gene. Overexpression of Nlp enhances the malignant progression of ERa-positive breast cancer cells in vitro, whereas knockdown of Nip suppresses this biological effects in ERa-positive breast cancer ceils. ERa/NIp axis may serve as a promising target against breast cancer.

Ethanolic extract of dandelion(Taraxacum mongolicum) induces estrogenic activity in MCF-7 cells and immature rats

Plants of the genus Taraxacum, commonly known as dandelions, are used to treat breast cancer in traditional folk medicine. However, their use has mainly been based on empirical findings without sufficient scientific evidence. Therefore, we hypothesized that dandelions would behave as a Selective estrogen receptor modulator （SERM） and be effective as hormone replacement therapy （HRT） in the postmenopausal women. In the present study, in vitro assay systems, including cell proliferation assay, reporter gene assay, and RT-PCR to evaluate the mRNA expression of estrogen-related genes （pS2 and progesterone receptor, PR）, were performed in human breast cancer cells. Dandelion ethanol extract （DEE） significantly increased cell proliferation and estrogen response element （ERE）-driven luciferase activity. DEE significantly induced the expression of estrogen related genes such as pS2 and PR, which was inhibited by tamoxifen at 1 gmol L-1. These results indicated that DEE could induce estrogenic activities mediated by a classical estrogen receptor pathway. In addition, immature rat uterotrophic assay was carried out to identify estrogenic activity of DEE in vivo. The lowest concentration of DEE slightly increased the uterine wet weight, but there was no significant effect with the highest concentration of DEE. The results demonstrate the potential estrogenic activities of DEE, providing scientific evidence supporting their use in traditional medicine.

Estrogenic activity of osthole and imperatorin in MCF-7 cells and their osteoblastic effects in Saos-2 cells

There is an increasing interest in phytoestrogens due to their potential medical usage in hormone replacement therapy(HRT). The present study was designed to investigate the in vitro effects of estrogen-like activities of two widespread coumarins, osthole and imperatorin, using the MCF-7 cell proliferation assay and their alkaline phosphatase(ALP) activities in osteoblasts Saos-2 cells. The two compounds were found to strongly stimulate the proliferation of MCF-7 cells. The estrogen receptor-regulated ERα, progesterone receptor(PR) and PS2 m RNA levels were increased by treatment with osthole and imperatorin. All these effects were significantly inhibited by the specific estrogen receptor antagonist ICI182, 780. Cell cycle analysis revealed that their proliferation stimulatory effect was associated with a marked increase in the number of MCF-7 cells in S phase, which was similar to that observed with estradiol. It was also observed that they significantly increased ALP activity, which was reversed by ICI182,780. These results suggested that osthole and imperatorin could stimulate osteoblastic activity by displaying estrogenic properties or through the ER pathway. In conclusion, osthole and imperatorin may represent new pharmacological tools for the treatment of osteoporosis.

Medical applications of phytoestrogens from the Thai herb Pueraria mirifica

Pueraria mirifica Airy Shaw et Suvatabandhu is a medicinal plant endemic to Thailand.It has been used in Thai folklore medicine for its rejuvenating qualities in aged women and men for nearly one hundred years.Indeed,it has been claimed that P.mirifica contains active phytoestrogens(plant substances with estrogen-like activity).Using high performance liquid chromatography,at least 17 phytoestrogens,mainly isoflavones,have been isolated.Thus,fairly considerable scientific researches,both in vitro in cell lines and in vivo in various species of animals including humans,have been conducted to date to address its estrogenic activity on the reproductive organs,bones,cardiovascular diseases and other climacteric related symptoms.The antioxidative capacity and antiproliferative effect on tumor cell lines have also been assessed.In general,P.mirifica could be applicable for preventing,or as a therapeutic for,the symptoms related to estrogen deficiency in menopausal women as well as in andropausal men.However,the optimal doses for each desirable effect and the balance to avoid undesired side effects need to be calculated before use.

Antifertility activity of Artemisia vulgaris leaves on female Wistar rats

AIM： To evaluate the antifertility activity of Artemisia vulgar＆ leaves on female Wistar rats. METHOD： The plant extract was tested for its effect on implant formation at two dose levels, 300 and 600 mg.kg 1, respectively. The effective methanolic plant extract was further studied for estrogenic potency on ovariectomised immature female Wistar rats. RESULTS： The data presented in this study demonstrate the antifertility potential of Artemisia vulgar＆ methanolic leaf extract, which shows a strong and significant decrease in implant formation （100%）, and a strong estrogenic effect resulting in a significant increase in uterine weight in immature ovariectomised rats. These observations suggest that the methanolic extract of Artemisia vulgaris leaves has strong anti-implantation activity and estrogenic activity. CONCLUSION： The methanolic plant extract ofA. vulgaris has antifertility activity.