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2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) inhibits human ovarian cancer cell proliferation

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Abstract

Purpose

The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, mediates a broad spectrum of biological processes, including ovarian growth and ovulation. Recently, we found that an endogenous AhR ligand (ITE) can inhibit ovarian cancer proliferation and migration via the AhR. Here, we tested whether 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, an exogenous AhR ligand) may exert similar anti-ovarian cancer activities using human ovarian cancer and non-cancerous human ovarian surface epithelial cells.

Methods

Two human ovarian cancer cell lines (SKOV-3 and OVCAR-3) and one human ovarian surface epithelial cell line (IOSE-385) were used. Cell proliferation and migration activities were determined using crystal violet and FluoroBlok insert system assays, respectively. AhR protein expression was assessed by Western blotting. Expression of cytochrome P450, family 1, member A1 (CYP1A1) and member B1 (CYP1B1) mRNA was assessed by qPCR. Small interfering RNAs (siRNAs) were used to knock down AhR expression.

Results

We found that TCDD dose-dependently suppressed OVCAR-3 cell proliferation, with a maximum effect (~70 % reduction) at 100 nM. However, TCDD did not affect SKOV-3 and IOSE-385 cell proliferation and migration. The estimated IC50 of TCDD for inhibiting OVCAR-3 cell proliferation was 4.6 nM. At 10 nM, TCDD time-dependently decreased AhR protein levels, while it significantly increased CYP1A1 and CYP1B1 mRNA levels in SKOV-3, OVCAR-3 and IOSE-385 cells, indicating activation of AhR signaling. siRNA-mediated AhR knockdown readily blocked TCDD-mediated suppression of OVCAR-3 cell proliferation.

Conclusion

Our data indicate that TCDD can suppress human ovarian cancer cell proliferation via the AhR signaling pathway and that TCDD exhibits an anti-proliferative activity in at least a subset of human ovarian cancer cells.

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Acknowledgment

This work was supported in part by the US National Institutes of Health grant PO1 HD38843 to R.R. Magness, I.M. Bird, and J. Zheng, a Department of Obstetrics/Gynecology R & D Grant, University of Wisconsin-Madison to J. Zheng, and the National Science Foundation of China grants No. 81100429 and 81270703 to K. Wang

Conflict of Interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, University of Wisconsin, 202 S. Park St., Madison, WI, 53715, USA

    Yan Li, Yi-Zhou Jiang, Cai-Feng Dai & Jing Zheng

  2. Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, 200040, China

    Kai Wang & Xin-Wen Chang

  3. Center for Reproductive Medicine, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, China

    Cai-Feng Dai

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  1. Yan Li
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Correspondence to Jing Zheng.

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Yan Li and Kai Wang are contributed equally

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Li, Y., Wang, K., Jiang, YZ. et al. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) inhibits human ovarian cancer cell proliferation. Cell Oncol. 37, 429–437 (2014). https://doi.org/10.1007/s13402-014-0206-4

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