Nickel’s Role in Pancreatic Ductal Adenocarcinoma: Potential Involvement of microRNAs

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancer types with a limited overall survival rate due to the asymptomatic progression of symptoms in metastatic stages of the malignancy and the lack of an early reliable diagnostic biomarker. MicroRNAs (miRs/miRNAs) are small (~18–24 nucleotides), endogenous, non-coding RNAs, which are closely linked to the development of numerous malignancies comprising PDAC. Recent studies have described the role of environmental pollutants such as nickel (Ni) in PDAC, but the mechanisms of Ni-mediated toxicity in cancer are still not completely understood. Specifically, Ni has been found to alter the expression and function of miRs in several malignancies, leading to changes in target gene expression. In this study, we found that levels of Ni were significantly higher in cancerous tissue, thus implicating Ni in pancreatic carcinogenesis. Hence, in vitro studies followed by using both normal and pancreatic tumor cell lines and increasing Ni concentration increased lethality. Comparing LC50 values, Ni-acetate groups demonstrated lower values needed than in NiCl2 groups, suggesting greater Ni-acetate. Panc-10.05 cell line appeared the most sensitive to Ni compounds. Exposure to Ni-acetate resulted in an increased phospho-AKT, and decreased FOXO1 expression in Panc-10.05 cells, while NiCl2 also increased PTEN expression in Panc-10.05 cells. Specifically, following NiCl2 exposure to PDAC cells, the expression levels of miR-221 and miR-155 were significantly upregulated, while the expression levels of miR-126 were significantly decreased. Hence, our study has suggested pilot insights to indicate that the environmental pollutant Ni plays an important role in the progression of PDAC by promoting an association between miRs and Ni exposure during PDAC pathogenesis

Epigenetic mechanisms in metal carcinogenesis

Many metals exhibit genotoxic and/or carcinogenic effects. These toxic metals can be found ubiquitously – in drinking water, food, air, general use products, in everyday and occupational settings. Exposure to such carcinogenic metals can result in serious health disorders, including cancer. Arsenic, cadmium, chromium, nickel, and their compounds have already been recognized as carcinogens by the International Agency for Research on Cancer. This review summarizes a wide range of epigenetic mechanisms contributing to carcinogenesis induced by these metals, primarily including, but not limited to, DNA methylation, miRNA regulation, and histone posttranslational modifications. The mechanisms are described and discussed both from a metal-centric and a mechanism-centric standpoint. The review takes a broad perspective, putting the mechanisms in the context of real-life exposure, and aims to assist in guiding future research, particularly with respect to the assessment and control of exposure to carcinogenic metals and novel therapy development

A meta-analysis excerpt: Is exposure to environmental pollutants associated with pancreatic cancer?

Istraživanje u oblasti karcinoma pankreasa i zagađivača iz životne sredine sve je intenzivnije. Za neke od ovih zagađivača pretpostavlja se da su povezani sa nastankom ili progresijom karcinoma pankreasa. Nijedna meta-analiza o povezanosti navedenog nije sprovedena, dok bi rezultati iste mogli pomoći u tumačenju dostupnih podataka i usmeravanju budućeg istraživanja. ...There is a rise in research on the connection between pancreatic cancer and environmental pollutants. Some of these pollutants are assumed to be associated with the onset or progression of pancreatic cancer. No meta-analyses summarizing the association between these two have been conducted yet, while the results of such an analysis could help interpret current and guide future research. ..

Sulforaphane and sulforaphane - glucosinolate toxicity prediction using the in silico US-EPA COMPTOX chemicals DASHBOARD method

In silico metode u toksikologiji podrazumevaju upotrebu kompjuterskih metoda koje omogućavaju analizu i predviđanje toksičnosti supstanci, pri čemu mogu usmeriti dalja eksperimentalna istraživanja. Sulforafan (SFN) je organosumporna supstanca iz grupe izotiocijanata, prisutna u povrću krstašica. Dok se SFN-glukozinolat ekstrahuje iz brokolija i uključen je u brojne kliničke studije, SFN je hemijski sintetisan i koristi se samo u istraživačke svrhe. ...In silico methods in toxicology use computer methods to analyze and predict the toxicity of substances, which can serve as a basis for further experimental studies. Sulforaphane (SFN) is an organosulfur chemical from the isothiocyanate group, present in cruciferous vegetables. While SFN-glucosinolate is extracted from broccoli and is presently ongoing numerous clinical studies, SFN has been chemically synthetized, currently only for research purposes. ..

Informed mom, healthy baby - How to live safely with chemicals

Poslednjih decenija prošlog veka naučnici su utvrdili da pojedine hemikalije, mogu uticati na brojne sisteme organa i izazvati štetne efekte po naše zdravlje. Među hemikalijama sa kojima dolazimo u kontakt gotovo svakodnevno, posebno mesto zauzimaju hemikalije koje mogu delovati na endokrini sistem. ...In the last decades of the twentieth century, scientists have observed that exposure to certain, human-made chemicals can affect numerous organ systems and cause harmful effects on our health. Among the chemicals hiding in everyday products, substances of special concern are those that can affect the endocrine system. ..