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Effect of bisphenols on telomerase expression and activity in breast cancer cell lines

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Abstract

Bisphenol A (BPA), a monomer of polycarbonates and resins, was shown to induce the expression of telomerase enzyme which has been associated with breast cancer development and progression. However, the effects of BPA analogues, bisphenol F (BPF) and bisphenol S (BPS) on telomere-linked pathway have not been evaluated. Herein, MCF-7 (estrogen receptor (ER)-positive) and MDA-MB-231 (ER-negative) cells were treated with BPA, BPF and BPS ± estrogen receptor inhibitor (ERI), for 24 and/or 48 h. RNA expression and enzymatic activity of telomerase were measured using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and telomeric repeat amplification protocol (TRAP); respectively. Relative telomere length (RTL) was also measured using quantitative PCR. After 24 h, the three bisphenols resulted in a 2–3 folds increase in expression and activity of telomerase in MCF-7 but not in MDA-MB-231 cells, and this increase was prevented upon co-treatment with ERI. The observed increase in the expression and activity of telomerase after 24 h of treatment with bisphenols was associated with differential and modest ER-dependent lengthening in RTL at 48 h. Our results show that telomerase potentially mediates the effects of the three bisphenols in ER-positive breast carcinoma. Hence, further investigation is warranted to elucidate the telomerase-linked pathways that could underlie bisphenol-related effects.

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Funding

This work was supported by the American University of Beirut Faculty of Medicine Medical Practice Plan grant given to N.K.Z. The authors would like to acknowledge the National Council for Scientific Research of Lebanon (CNRS-L) for granting a doctoral fellowship to Z.A. R.N. is a member of the International Breast Cancer and Nutrition (IBCN). The funding sources were not involved in the study design, data collection and analysis or the manuscript writing and submission.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Riad El-Solh, Beirut, 1107-2020, Lebanon

    Zainab Awada, Reem Akika & Nathalie K. Zgheib

  2. Department of Anatomy, Cell Biology and Physiology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon

    Rihab Nasr

  3. Epigenetics Group, International Agency for Research On Cancer, Lyon, France

    Akram Ghantous

  4. Department of Preventive Medicine, Northwestern University, Chicago, USA

    Lifang Hou

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  1. Zainab Awada
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  2. Rihab Nasr
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  4. Akram Ghantous
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  5. Lifang Hou
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  6. Nathalie K. Zgheib
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Contributions

Conceptualization, methodology and data interpretation (ZA, RN, LH, AG, NK-Z); Experiments (ZA, RA); Supervision (RN, AG, NK-Z); Analysis (ZA, RA, RN, AG, NK-Z); Writing (ZA, NK-Z); Funding acquisition (NK-Z). All authors approved final version of the manuscript.

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Correspondence to Nathalie K. Zgheib.

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Awada, Z., Nasr, R., Akika, R. et al. Effect of bisphenols on telomerase expression and activity in breast cancer cell lines. Mol Biol Rep 47, 3541–3549 (2020). https://doi.org/10.1007/s11033-020-05444-0

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