Long-lasting subclinical inflammation is associated with a wide range of human diseases, particularly at a middle and older age. Recent reports showed that there is a direct causal link between inflammation and cancer development, as several cancers were found to be associated with chronic inflammatory conditions. In patients with cancer, healthy endothelial cells regulate vascular homeostasis, and it is believed that they can limit tumor growth, invasiveness, and metastasis. Conversely, dysfunctional endothelial cells that have been exposed to the inflammatory tumor microenvironment can support cancer progression and metastasis. Dysfunctional endothelial cells can exert these effects via diverse mechanisms, including dysregulated adhesion, permeability, and activation of NF-κB and STAT3 signaling. In this review, we highlight the role of vascular inflammation in predisposition to cancer within the context of two common disease risk factors: obesity and smoking. In addition, we discuss the molecular triggers, pathophysiological mechanisms, and the biological consequences of vascular inflammation during cancer development and metastasis. Finally, we summarize the current therapies and pharmacological agents that target vascular inflammation and endothelial dysfunction.

There is an ample epidemiological evidence to support the role of environmental contaminants such as bisphenol A (BPA) in breast cancer development but the molecular mechanisms of their action are still not fully understood. Therefore, we sought to analyze the effects of three common contaminants (BPA; 4-tert-octylphenol, OP; hexabromocyclododecane, HBCD) on mammary epithelial cell (HME1) and MCF7 breast cancer cell line. We also supplied some data on methoxychlor, MXC; 4-nonylphenol, NP; and 2-amino-1-methyl-6-phenylimidazo [4–b] pyridine, PhIP. We focused on testing the prolonged (two months) exposure to low nano-molar concentrations (0.0015–0.0048 nM) presumed to be oncogenic and found that they induced DNA damage (evidenced by upregulation of pH2A.X, pCHK1, pCHK2, p-P53) and disrupted the cell cycle. Some agents induced epigenetic (methylation) changes of tumor suppressor genes TIMP3, CHFR, ESR1, IGSF4, CDH13, and GSTP1. Obviously, the accumulation of these molecular alterations is an essential base for cancer development. Consistent with this, we observed that these agents increased cellular invasiveness through collagen. Cellular abilities to form colonies in soft agar were increased for MCF7. Toxic agents induced phosphorylation of protein kinase such as EGFR, CREB, STAT6, c-Jun, STAT3, HSP6, HSP27, AMPKα1, FAK, p53, GSK-3α/β, and P70S6 in HME1. Most of these proteins are involved in potential oncogenic pathways. Overall, these data clarify the molecular alterations that can be induced by some common environmental contaminants in mammary epithelial cells which could be a foundation to understand environmental carcinogenesis.

Colorectal cancer is a common cancer with a poor prognosis in both males and females. The influence of bisphenol A (BPA), a widely used environmental contaminant, in colon cancer development and progression is not well identified, in spite of the fact that the most common mode of exposure to BPA is ingestion. The aim of this work is to elucidate the carcinogenic effects of BPA in the colon in vitro. We analyzed BPA’s effects on human colon epithelial (HCoEpiC) and colon cancer (HCT116) cells. BPA exerted cytotoxic effects and augmented the 5FU cytotoxicity on both cell lines at high doses, while it did not show this effect at low doses. Therefore, we focused on studying the effects of low-dose (0.0043 nM) exposure on normal colonic epithelial cells for a long period of time (two months), which is more consistent with environmental exposure levels and patterns. BPA increased cellular invasiveness through collagen and the ability to anchorage-independent cell growth, as measured by colony formation in soft agar, which could support oncogenicity. To gain insights into the mechanism of these actions, we performed transcriptomic analysis using next-generation sequencing, which revealed 340 differentially expressed transcripts by BPA in HCT116 and 75 in HCoEpiC. These transcripts belong in many cancer-related pathways such as apoptosis, cell proliferation, signal transduction, and angiogenesis. Some of the significant genes (FAM83H, CXCL12, PITPNA, HMOX1, DGKZ, NR5A2, VMP1, and ID1) were confirmed by quantitative RT-PCR. Furthermore, BPA induced the phosphorylation of protein kinases such as JNK1/2/3, GSK-3α/β, AMPKα1, AKT1/2/3, AMPKα2, HSP27, β-catenin, STAT2, Hck, Chk2, FAK, and PRAS40 in HCoEpiC, as well as GSK-3α/β, p53, AKT1/2/3, p70 S6 kinase, and WNK1 in HCT116. The majority of these proteins are involved in potential carcinogenic pathways. Taken together, these data suggest that BPA plays a role in colon carcinogenesis, and they provide insights into the molecular mechanisms of colon epithelial cell transformation by BPA. Increasing exposure to environmental toxins such as BPA can explain the increasing incidence of colorectal cancer.