Mechanisms of environmental chemicals that enable the cancer hallmark of evasion of growth suppression

Abstract

As part of the Halifax Project, this review brings attention to the potential effects of environmental chemicals on important molecular and cellular regulators of the cancer hallmark of evading growth suppression. Specifically, we review the mechanisms by which cancer cells escape the growth-inhibitory signals of p53, retinoblastoma protein, transforming growth factor-beta, gap junctions and contact inhibition. We discuss the effects of selected environmental chemicals on these mechanisms of growth inhibition and cross-reference the effects of these chemicals in other classical cancer hallmarks.

Associations of persistent organic pollutants in serum and adipose tissue with breast cancer prognostic markers

“…POP levels in our study were negatively associated with p53 expression, in a dose-dependent manner in the case of adipose tissue HCB concentrations (significant trend) and showing a non-significant trend in the case of PCB-138 concentrations. It has been suggested that certain POPs can downregulate p53 expression by interaction with its negative regulator MDM2 or by the disruption of p53 phosphorylation, stabilization, and function (Nahta et al, 2015). Our results are consistent with the experimental Fig.…”

“…Tumor suppressor oncogene p53 prevents neoplastic development by inhibiting the proliferation of abnormal cells (Gasco et al, 2002), and it is noteworthy that a mutation in this oncogene is observed in almost 50% of cancers (Nahta et al, 2015). POP levels in our study were negatively associated with p53 expression, in a dose-dependent manner in the case of adipose tissue HCB concentrations (significant trend) and showing a non-significant trend in the case of PCB-138 concentrations.…”

“…It has also been reported that POPs may not necessarily cause cancer themselves but may act as co-carcinogens (Landau-Ossondo et al, 2009). Thus, Johnson et al (2012) found that p,p′-DDE promoted but did not induce carcinogenesis in experimental models, while various authors reported that some OCPs significantly reduce the survival of breast cancer patients (Hoyer et al, 2000;Parada et al, 2015) and that chronic exposure can negatively affect the growth inhibition system that commonly downregulates the cell cycle in abnormal conditions (Nahta et al, 2015). It has also been suggested that POPs might be associated with cancer development by mechanisms unrelated to estrogen receptors, such as the induction of oxidative stress (Arrebola et al, 2014).…”

Health effects of desalinated water: Role of electrolyte disturbance in cancer development

“…The list of processes that are controlled by cell volume and osmotic stress reads like the book of life itself -it includes growth and proliferation, membrane transport, exocytosis, endocytosis, cell shape changes, hormone signaling, metabolism, excitability, neural communication, cell migration, nutrient delivery, waste filtration, necrosis and apoptosis (Casey et al, 2015;Nahta et al, 2015). These are among the common hallmarks of cancer (Hanahan and Weinberg, 2011).…”

“…Therefore, in a paradoxical manner, the same DNA repair pathways that are charged with preventing damage from being fixed to carcinogenic mutations may promote the survival of an initiated but damaged cell (Langie et al, 2015;Casey et al, 2015). Many metals (such as lead, nickel, cobalt and mercury) are pro-carcinogenic in their ability to promote genomic instability, while simultaneously being anticarcinogenic in their ability to promote apoptosis (Hu et al, 2015;Nahta et al, 2015). Thus, like many low-dose contaminants in the environment, electrolyte disturbance can exercise predisposing influence towards the hallmarks of cancer by a wide variety of mechanisms, including genomic changes, oncogene expression, modification of signal transduction and even hypoxia.…”