Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Cellular Oncology
Published in: Cellular Oncology 6/2014

01-12-2014 | Original Paper

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

Authors: Yan Li, Kai Wang, Yi-Zhou Jiang, Xin-Wen Chang, Cai-Feng Dai, Jing Zheng

Published in: Cellular Oncology | Issue 6/2014

Login to get access

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.
Literature
1.
T.A. Yap, C.P. Carden, S.B. Kaye, Beyond chemotherapy: targeted therapies in ovarian cancer. Nat. Rev. Cancer 9, 167–181 (2009)PubMedCrossRef
2.
J. Di, T. Duiveman-de Boer, P.L. Zusterzeel, C.G. Fig, L.F. Massuger, R. Torensma, The stem cell markers Oct4A, Nanog and c-Myc are expressed in ascites cells and tumor tissue of ovarian cancer patients. Cell. Oncol. 36, 363–374 (2013)
3.
O. Krijgsman, D. Israeli, H.F. van Essen, P.P. Eijk, M.L. Berens, C.H. Mellink, A.W. Nieuwint, M.M. Weiss, R.D. Steenbergen, G.A. Meijer, B. Ylstra, Detection limits of DNA copy number alterations in heterogeneous cell populations. Cell. Oncol. 36, 27–36 (2013)CrossRef
4.
R.C. Jr, B. Bast, G.B.M. Hennessy, The biology of ovarian cancer: new opportunities for translation. Nat. Rev. Cancer 9, 415–428 (2009)CrossRef
5.
S. Safe, A. McDougal, Mechanism of action and development of selective aryl hydrocarbon receptor modulators for treatment of hormone-dependent cancers (review). Int. J. Oncol. 20, 1123–1128 (2002)PubMed
6.
I. Hernandez-Ochoa, B.N. Karman, J.A. Flaws, The role of the aryl hydrocarbon receptor in the female reproductive system. Biochem. Pharmacol. 77, 547–559 (2009)PubMedCentralPubMedCrossRef
7.
Y. Fujii-Kuriyama, K. Kawajiri, Molecular mechanisms of the physiological functions of the aryl hydrocarbon (dioxin) receptor, a multifunctional regulator that senses and responds to environmental stimuli. Proc. Jpn. Acad. Ser. B Phys. Biol. Sci. 86, 40–53 (2010)PubMedCentralPubMedCrossRef
8.
R.W. Clapp, M.M. Jacobs, E.L. Loechler, Environmental and occupational causes of cancer: new evidence 2005–2007. Rev. Environ. Health 23, 1–37 (2008)PubMedCentralPubMedCrossRef
9.
E. Diamanti-Kandarakis, J.P. Bourguignon, L.C. Giudice, R. Hauser, G.S. Prins, A.M. Soto, R.T. Zoeller, A.C. Gore, Endocrine-disrupting chemicals: an endocrine society scientific statement. Endocr. Rev. 30, 293–342 (2009)PubMedCentralPubMedCrossRef
10.
P.A. Bertazzi, C. Zocchetti, S. Guercilena, D. Consonni, A. Tironi, M.T. Landi, A.C. Pesatori, Dioxin exposure and cancer risk: a 15-year mortality study after the “Seveso accident”. Epidemiology 8, 646–652 (1997)PubMed
11.
J.F. Viel, M.C. Clement, M. Hagi, S. Grandjean, B. Challier, A. Danzon, Dioxin emissions from a municipal solid waste incinerator and risk of invasive breast cancer: a population-based case–control study with GIS-derived exposure. Int. J. Health Geogr. 7, 4 (2008)PubMedCentralPubMedCrossRef
12.
K. Steenland, P. Bertazzi, A. Baccarelli, M. Kogevinas, Dioxin revisited: developments since the 1997 IARC classification of dioxin as a human carcinogen. Environ. Health Perspect. 112, 1265–1268 (2004)PubMedCentralPubMedCrossRef
13.
P. Lin, H. Chang, W.T. Tsai, M.H. Wu, Y.S. Liao, J.T. Chen, J.M. Su, Overexpression of aryl hydrocarbon receptor in human lung carcinomas. Toxicol. Pathol. 31, 22–30 (2003)PubMedCrossRef
14.
D.B. McGregor, C. Partensky, J. Wilbourn, J.M. Rice, An IARC evaluation of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans as risk factors in human carcinogenesis. Environ. Health Perspect. 106 (Suppl 2), 755–760 (1998)PubMedCentralPubMedCrossRef
15.
D. Consonni, A.C. Pesatori, C. Zocchetti, R. Sindaco, L.C. D’Oro, M. Rubagotti, P.A. Bertazzi, Mortality in a population exposed to dioxin after the Seveso, Italy, accident in 1976: 25 years of follow-up. Am. J. Epidemiol. 167, 847–858 (2008)
16.
R.J. Kociba, D.G. Keyes, J.E. Beyer, R.M. Carreon, C.E. Wade, D.A. Dittenber, R.P. Kalnins, L.E. Frauson, C.N. Park, S.D. Barnard, R.A. Hummel, C.G. Humiston, Results of a two-year chronic toxicity and oncogenicity study of 2,3,7,8-tetrachlorodibenzo-p-dioxin in rats. Toxicol. Appl. Pharmacol. 46, 279–303 (1978)PubMedCrossRef
17.
J. Zhang, H. Zong, S. Li, D. Zhang, L. Zhang, Q. Xia, Activation of aryl hydrocarbon receptor suppresses invasion of esophageal squamous cell carcinoma cell lines. Tumori 98, 152–157 (2012)PubMed
18.
S. Zhang, P. Lei, X. Liu, X. Li, K. Walker, L. Kotha, C. Rowlands, S. Safe, The aryl hydrocarbon receptor as a target for estrogen receptor-negative breast cancer chemotherapy. Endocr. Relat. Cancer. 16, 835–844 (2009)PubMedCentralPubMedCrossRef
19.
A. Koliopanos, J. Kleeff, Y. Xiao, S. Safe, A. Zimmermann, M.W. Buchler, H. Friess, Increased arylhydrocarbon receptor expression offers a potential therapeutic target for pancreatic cancer. Oncogene 21, 6059–6070 (2002)PubMedCrossRef
20.
F.J. Quintana, G. Murugaiyan, M.F. Farez, M. Mitsdoerffer, A.M. Tukpah, E.J. Burns, H.L. Weiner, An endogenous aryl hydrocarbon receptor ligand acts on dendritic cells and T cells to suppress experimental autoimmune encephalomyelitis. Proc. Natl. Acad. Sci. U. S. A. 107, 20768–20773 (2010)PubMedCentralPubMedCrossRef
21.
K. Wang, Y. Li, Y.Z. Jiang, C.F. Dai, M.S. Patankar, J.S. Song, J. Zheng, An endogenous aryl hydrocarbon receptor ligand inhibits proliferation and migration of human ovarian cancer cells. Cancer Lett. 340, 63–71 (2013)PubMedCentralPubMedCrossRef
22.
G.S. Hagopian, G.B. Mills, A.R. Khokhar, R.C. Jr, Z.H.S. Bast, Expression of p53 in cisplatin-resistant ovarian cancer cell lines: modulation with the novel platinum analogue (1R, 2R-diaminocyclohexane) (trans-diacetato) (dichloro)-platinum (IV). Clin. Cancer Res. 5, 655–663 (1999)PubMed
23.
K.M. Lau, S.C. Mok, S.M. Ho, Expression of human estrogen receptor-α and -β, progesterone receptor, and androgen receptor mRNA in normal and malignant ovarian epithelial cells. Proc. Natl. Acad. Sci. U. S. A. 96, 5722–5727 (1999)PubMedCentralPubMedCrossRef
24.
H.H. Li, Y.J. Zhao, Y. Li, D.F. Dai, S.O. Jobe, X.F. Li, X.S. Yang, M.S. Patankar, R.R. Magness, J. Zheng, Estradiol-17β and its metabolites attenuate vitamin c-suppressed human ovarian cancer cell proliferation. Reprod. Sci. 21, 102–111 (2014)PubMedCrossRef
25.
M. Boivin, D. Lane, A. Piche, C. Rancourt, Ca125 (MUC16) tumor antigen selectively modulates the sensitivity of ovarian cancer cells to genotoxic drug-induced apoptosis. Gynecol. Oncol. 115, 407–413 (2009)PubMedCrossRef
26.
C.F. Dai, Y.Z. Jiang, Y. Li, K. Wang, P.S. Liu, M.S. Patankar, J. Zheng, Expression and roles of slit/robo in human ovarian cancer. Histochem. Cell Biol. 135, 475–485 (2011)PubMedCentralPubMedCrossRef
27.
Y.M. Wu, X. Chen, Q. Zhou, Q.Z. He, J.H. Kang, J. Zheng, K. Wang, T. Duan, ITE and TCDD differentially regulate the vascular remodeling of rat placenta via the activation of AhR. PLoS One 9, e86549 (2014)PubMedCentralPubMedCrossRef
28.
D.P. Bofinger, L. Feng, L.H. Chi, J. Love, F.D. Stephen, T.R. Sutter, K.G. Osteen, T.G. Costich, R.E. Batt, S.T. Koury, J.R. Olson, Effect of TCDD exposure on CYP1A1 and CYP1B1 expression in explant cultures of human endometrium. Toxicol. Sci. 62, 299–314 (2001)PubMedCrossRef
29.
J.A. Pitt, L. Feng, B.D. Abbott, J. Schmid, R.E. Batt, T.G. Costich, S.T. Koury, D.P. Bofinger, Expression of AhR and ARNT mRNA in cultured human endometrial explants exposed to TCDD. Toxicol. Sci. 62, 289–298 (2001)PubMedCrossRef
30.
M.D. Mueller, J.L. Vigne, M. Streich, M.K. Tee, L. Raio, E. Dreher, N.A. Bersinger, R.N. Taylor, 2,3,7,8-Tetrachlorodibenzo-p-dioxin increases glycodelin gene and protein expression in human endometrium. J. Clin. Endocrinol. Metab. 90, 4809–4815 (2005)PubMedCrossRef
31.
Y.Z. Jiang, Y. Li, K. Wang, C.F. Dai, S.A. Huang, D.B. Chen, J. Zheng, Distinct roles of HIF1A in endothelial adaptations to physiological and ambient oxygen. Mol. Cell. Endocrinol. 391, 60–67 (2014)PubMedCrossRef
32.
Y.Z. Jiang, K. Wang, R. Fang, J. Zheng, Expression of aryl hydrocarbon receptor in human placentas and fetal tissues. J. Histochem. Cytochem. 58, 679–685 (2010)PubMedCentralPubMedCrossRef
33.
S.H. Juan, J.L. Lee, P.Y. Ho, Y.H. Lee, W.S. Lee, Antiproliferative and antiangiogenic effects of 3-methylcholanthrene, an aryl-hydrocarbon receptor agonist, in human umbilical vascular endothelial cells. Eur. J. Pharmacol. 530, 1–8 (2006)PubMedCrossRef
34.
M. Wormke, E. Castro-Rivera, I. Chen, S. Safe, Estrogen and aryl hydrocarbon receptor expression and crosstalk in human ishikawa endometrial cancer cells. J. Steroid Biochem. Mol. Biol. 72, 197–207 (2000)PubMedCrossRef
35.
A. McDougal, M.S. Gupta, D. Morrow, K. Ramamoorthy, J.E. Lee, S.H. Safe, Methyl-substituted diindolylmethanes as inhibitors of estrogen-induced growth of t47d cells and mammary tumors in rats. Breast Cancer Res. Treat. 66, 147–157 (2001)PubMedCrossRef
36.
J.M. Hall, M.A. Barhoover, D. Kazmin, D.P. McDonnell, W.F. Greenlee, R.S. Thomas, Activation of the aryl-hydrocarbon receptor inhibits invasive and metastatic features of human breast cancer cells and promotes breast cancer cell differentiation. Mol. Endocrinol. 24, 359–369 (2010)PubMedCentralPubMedCrossRef
37.
A. Geurts van Kessel, The cancer genome: from structure to function. Cell. Oncol. 37, 155–165 (2014)
38.
E.A. Stevens, J.D. Mezrich, C.A. Bradfield, The aryl hydrocarbon receptor: a perspective on potential roles in the immune system. Immunology 127, 299–311 (2009)PubMedCentralPubMedCrossRef
39.
A. Puga, C. Ma, J.L. Marlowe, The aryl hydrocarbon receptor cross-talks with multiple signal transduction pathways. Biochem. Pharmacol. 77, 713–722 (2009)PubMedCentralPubMedCrossRef
40.
Z. Tan, X. Chang, A. Puga, Y. Xia, Activation of mitogen-activated protein kinases (MAPKs) by aromatic hydrocarbons: role in the regulation of aryl hydrocarbon receptor (AHR) function. Biochem. Pharmacol. 64, 771–780 (2002)PubMedCrossRef
41.
Z. Tan, M. Huang, A. Puga, Y. Xia, A critical role for map kinases in the control of ah receptor complex activity. Toxicol. Sci. 82, 80–87 (2004)PubMedCrossRef
42.
R. Wu, L. Zhang, M.S. Hoagland, H.I. Swanson, Lack of the aryl hydrocarbon receptor leads to impaired activation of AKT/protein kinase B and enhanced sensitivity to apoptosis induced via the intrinsic pathway. J. Pharmacol. Exp. Ther. 320, 448–457 (2007)PubMedCrossRef
43.
E.C. Henry, J.C. Bemis, O. Henry, A.S. Kende, T.A. Gasiewicz, A potential endogenous ligand for the aryl hydrocarbon receptor has potent agonist activity in vitro and in vivo. Arch. Biochem. Biophys. 450, 67–77 (2006)PubMedCrossRef
44.
J. Song, M. Clagett-Dame, R.E. Peterson, M.E. Hahn, W.M. Westler, R.R. Sicinski, H.F. DeLuca, A ligand for the aryl hydrocarbon receptor isolated from lung. Proc. Natl. Acad. Sci. U. S. A. 99, 14694–14699 (2002)PubMedCentralPubMedCrossRef
45.
Y. Fan, G.P. Boivin, E.S. Knudsen, D.W. Nebert, Y. Xia, A. Puga, The aryl hydrocarbon receptor functions as a tumor suppressor of liver carcinogenesis. Cancer Res. 70, 212–220 (2010)PubMedCentralPubMedCrossRef
Metadata
Title
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) inhibits human ovarian cancer cell proliferation
Authors
Yan Li
Kai Wang
Yi-Zhou Jiang
Xin-Wen Chang
Cai-Feng Dai
Jing Zheng
Publication date
01-12-2014
Publisher
Springer Netherlands
Published in
Cellular Oncology / Issue 6/2014
Print ISSN: 2211-3428
Electronic ISSN: 2211-3436
DOI
https://doi.org/10.1007/s13402-014-0206-4

Other articles of this Issue 6/2014

Cellular Oncology 6/2014 Go to the issue

Original Paper

E4BP4 is a repressor of epigenetically regulated SOSTDC1 expression in breast cancer cells

Original Paper

Deoxyhypusine synthase (DHPS) inhibitor GC7 induces p21/Rb-mediated inhibition of tumor cell growth and DHPS expression correlates with poor prognosis in neuroblastoma patients

Original Paper

Relationship between therapeutic efficacy of doxorubicin-transferrin conjugate and expression of P-glycoprotein in chronic erythromyeloblastoid leukemia cells sensitive and resistant to doxorubicin

Original Paper

Apoptosis induction by an analog of curcumin (BDMC-A) in human laryngeal carcinoma cells through intrinsic and extrinsic pathways

Original Paper

Somatic mutations of amino acid metabolism-related genes in gastric and colorectal cancers and their regional heterogeneity - a short report

Original Paper

Short hairpin RNA-mediated down-regulation of CENP-A attenuates the aggressive phenotype of lung adenocarcinoma cells
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits