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

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.

Spatial distribution, temporal variation and risks of parabens and their chlorinated derivatives in urban surface water in Beijing, China

“…However, more and more studies have demonstrated that parabens are an emerging group of endocrine-disrupting chemicals, which may modulate or disrupt the endocrine system to affect the reproductive system, cause immune dysfunction, and produce developmental and behavioral disorders (Kang et al, 2013;Karpuzoglu et al, 2013;Meeker et al, 2011;Oishi, 2002;Piao et al, 2014;Soni et al, 2005). In addition, several studies have reported that parabens were associated with breast cancer etiology, and lead to a potential increase in breast cancer incidence (Darbre et al, 2004;Darbre and Harvey, 2014;Harvey, 2004). Moreover, conventional toxicity tests also show that parabens were toxic to aquatic organisms, such as algae, invertebrate and fish (Bazin et al, 2010;Dobbins et al, 2009;Yamamoto et al, 2011).…”

Breast Cancer and Deodorants/Antiperspirants: a Systematic Review

“…Parabens also 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. The authors concluded that there is evidence that parabens could have alleged responsibility in the occurrence of breast cancer (18).…”

Cytochrome P450-inhibitory activity of parabens and phthalates used in consumer products

“…Consumer products that contain constituents with endocrine-disrupting activity, such as parabens, are associated with increased breast cancer incidence in women Harvey and Darbre, 2004;Darbre and Charles, 2010;Darbre and Harvey, 2014). It was reported that unchanged parabens were present in human urine, and also tissues (Ye et al, 2006).…”