Parabens can enable hallmarks and characteristics of cancer in human breast epithelial cells: a review of the literature with reference to new exposure data and regulatory status

• Published in: Journal of applied toxicology 2014-09, Vol.34 (9), p.925-938
• Main Authors: Darbre, Philippa D., Harvey, Philip W.
• Format: Article
• Language: English
• Subjects: Apoptosis; Binding; Biological Availability; Breast; Breast - cytology; Breast - drug effects; Breast - pathology; Breast cancer; Breast Neoplasms - pathology; Cancer; Cell Line, Tumor; Cell Proliferation - drug effects; Cellular biology; Chemicals; cosmetics; DNA Damage; endocrine disruption; Environmental Exposure; Epithelial Cells - drug effects; Exposure; Female; Genomic Instability; Grounds; hallmarks of cancer; Human; Humans; Inhibitors; oestrogen; Paraben; Parabens - pharmacokinetics; Parabens - toxicity; personal care products; Receptors, Estrogen - metabolism; Regulators; Tamoxifen - analogs & derivatives; Tamoxifen - pharmacology; TOR Serine-Threonine Kinases - genetics; TOR Serine-Threonine Kinases - metabolism; Toxicology
• ISSN: 0260-437X; 1099-1263
• DOI: 10.1002/jat.3027

ABSTRACT A framework for understanding the complexity of cancer development was established by Hanahan and Weinberg in their definition of the hallmarks of cancer. In this review, we consider the evidence that parabens can enable development in human breast epithelial cells of four of six of the basic hallmarks, one of two of the emerging hallmarks and one of two of the enabling characteristics. In Hallmark 1, parabens have been measured as present in 99% of human breast tissue samples, possess oestrogenic activity and can stimulate sustained proliferation of human breast cancer cells at concentrations measurable in the breast. In Hallmark 2, parabens can inhibit the suppression of breast cancer cell growth by hydroxytamoxifen, and through binding to the oestrogen‐related receptor gamma may prevent its deactivation by growth inhibitors. In Hallmark 3, in the 10 nm–1 μm range, parabens give a dose‐dependent evasion of apoptosis in high‐risk donor breast epithelial cells. In Hallmark 4, long‐term exposure (>20 weeks) to parabens leads to increased migratory and invasive activity in human breast cancer cells, properties that are linked to the metastatic process. As an emerging hallmark methylparaben has been shown in human breast epithelial cells to increase mTOR, a key regulator of energy metabolism. As an enabling characteristic parabens can cause DNA damage at high concentrations in the short term but more work is needed to investigate long‐term, low‐dose mixtures. The ability of parabens to enable multiple cancer hallmarks in human breast epithelial cells provides grounds for regulatory review of the implications of the presence of parabens in human breast tissue. Copyright © 2014 John Wiley & Sons, Ltd. This review summarises evidence that parabens can lead in human breast epithelial cells to development of 4/6 of the hallmarks, 1/2 of the emerging hallmarks and 1/2 of the enabling characterstics of cancer cells as defined by Hanahan and Weinberg in 2011 and can do so at concentrations which are not incompatible with levels measurable in some human breast tissues. Results are discussed in the context of new exposure data and the regulatory status of parabens.