NJK14013, a novel synthetic estrogen receptor-α agonist, exhibits estrogen receptor-independent, tumor cell-specific cytotoxicity

Kim,Hye-In; Kim,Taelim; Kim,Ji-Eun; Lee,Jun; Heo,Jinyuk; Lee,Na-Rae; Kim,Nam-Jung; Inn,Kyung-Soo

doi:10.3892/ijo.2015.3002

NJK14013, a novel synthetic estrogen receptor-α agonist, exhibits estrogen receptor-independent, tumor cell-specific cytotoxicity

Authors:
- Hye-In Kim
- Taelim Kim
- Ji-Eun Kim
- Jun Lee
- Jinyuk Heo
- Na-Rae Lee
- Nam-Jung Kim
- Kyung-Soo Inn
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Affiliations: Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Dongdaemun-gu, Seoul 130-701, Republic of Korea, Department of Pharmacy, College of Pharmacy, Kyung Hee University, Dongdaemun-gu, Seoul 130-701, Republic of Korea
Published online on: May 12, 2015 https://doi.org/10.3892/ijo.2015.3002
Pages: 280-286

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Abstract

Estrogens act through interactions with estrogen receptors (ERs) to play diverse roles in various pathophysiological conditions. A number of synthetic selective estrogen receptor modulators (SERMs), such as tamoxifen and raloxifene, have been developed and used to treat ER-related diseases, including breast cancer and osteoporosis. Here, we identified a novel compound, bis(4-hydroxyphenyl)methanone-O-isopentyl oxime, designated NJK14013, as an ER agonist. NJK14013 activated ER-dependent transcription in a concentration-dependent manner, while suppressing androgen receptor-dependent transcriptional activity. It induced the activation-related phosphorylation of ER and enhanced the transcription of growth regulation by estrogen in breast cancer 1 (GREB1), further supporting its ER-stimulating activity. NJK14013 exerted anti-proliferative effects on various cancer cell lines, including an ER-negative breast cancer cell line, suggesting that it is capable of suppressing the growth of cancer cells independent of its ER-modulating activity. In addition, NJK14013 treatment resulted in significant apoptotic death of MCF7 and Ishikawa cancer cells, but did not induce apoptosis in non-cancer human umbilical vein endothelial cells. Collectively, our findings demonstrate that NJK14013 is a novel SERM that can activate ER-mediated transcription in MCF7 cells and suppress the proliferation of various cancer cells, including breast cancer cells and endometrial cancer cells. These results suggest that NJK14013 has potential as a novel SERM for anticancer or hormone-replacement therapy with reduced risk of carcinogenesis.

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