194 A POTENTIAL ENDOCRINE-DISRUPTING CHEMICAL, 4-NONYLPHENOL, STIMULATED THE OVARIAN CANCER CELL GROWTH BY UPREGULATING CELL CYCLE VIA AN ESTROGEN RECEPTOR SIGNALING PATHWAY IN CELLULAR AND ANIMAL MODELS

Abstract

Nonylphenol (NP), a subset of the alkylphenols, is used as a surfactant (surface-active agent). Nonylphenol has been widely detected in waste water, which is a concern since it is toxic to many aquatic organisms. Also, NP has been classified as an endocrine-disrupting chemical because of weak ability to mimic oestrogen and in turn disrupt the natural balance of hormones in organisms. In this study, the estrogenic effect of NP was examined in ovarian cancer BG-1 cells expressing high levels of oestrogen receptors (ER) by a cell viability assay and semiquantitative reverse-transcription PCR (RT-PCR) in cellular and animal models of xenografted mice. A treatment of BG-1 cells with NP (10–8 to 10–5 M) resulted in an increase in their cell proliferation as 17-β oestradiol (E2) did. In addition, NP upregulated the expression levels of cell-cycle regulating genes (i.e. cyclin D1, which is a downstream target of ER). As a result, NP stimulated the proliferation of BG-1 cells via an increase of the cell cycle progression. In a xenografted mouse model transplanted with BG-1 ovarian cancer cells, E2 or NP treatment significantly increased the tumour proliferation compared as a vehicle (corn oil) for 10 weeks. These results were identified by the measurement of tumour volume and histological analysis on tumour masses by using H&E staining and BrdU incorporation assay. These results support that NP may have a weak estrogenic activity and increase risk of cancer proliferation in oestrogen-dependent cancers such as ovarian cancer. This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Ministry of Education, Science and Technology (MEST) of Korea government (no. 2011-0015385).