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- Title
2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) inhibits human ovarian cancer cell proliferation.
- Authors
Dai, Cai-Feng; Li, Yan; Jiang, Yi-Zhou; Zheng, Jing; Wang, Kai; Chang, Xin-Wen
- 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 IC 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.
- Subjects
TETRACHLORODIBENZODIOXIN; ARYL hydrocarbon receptors; OVARIAN cancer; CANCER genetics; CANCER cell migration; CANCER cell proliferation; OVARIAN cancer prevention; PHYSIOLOGY
- Publication
Cellular Oncology (2211-3428), 2014, Vol 37, Issue 6, p429
- ISSN
2211-3428
- Publication type
Article
- DOI
10.1007/s13402-014-0206-4