The Molecular Mechanisms of Tobacco in Cancer Pathogenesis

Abstract

Context: Studies have shown that cancer is a multi-factorial disease in its pathogenesis, in addition to genetic disorders, the effect of environmental factors can also be pointed. Among all environmental factors, tobacco that is considered as the leading cause of respiratory and cardiovascular disease plays a key role in cancer pathogenesis and progression. More than 5,000 chemicals and 62 carcinogenes have been detected in tobacco, which could contribute to tumorgenesis through activating oncogenes, inhibition of tumor suppressor genes, genetic and epigenetic changes, alteration of growth pathways, angiogenesis and metastasis. Evidence Acquisition: To access the articles, we used valid external and internal databases. In order to set the search formula with maximum collectivity, at the first step, the main keywords were characterized and then equivalent terms were identified using various sources. In order to retrieve the last research papers, searches were conducted constantly from 1970 until 2015. The obtained results were screened in terms of relevance and quality indicators such as proper research design, control groups, inclusion and exclusion criteria, and also the statistical analysis. Accordingly, 150 articles were obtained and finally 64 articles which were eligible and had high relevance to the topic were selected and reviewed. Results: This review explains the association between tobacco smoking and the incidence of different human cancers; also it focuses on molecular mechanisms through which carcinogenic chemicals in tobacco smoke promote cancer progression. Among multiple components of tobacco smoke, three carcinogens, including polycyclic aromatic hydrocarbons (PAH), nictotine and nicotin-derived nitrosamine ketone (NNK) convincingly play major roles in the pathogenesis of a wide range of cancers. In fact, these toxic and carcinogenic agents alter the expression of oncogenes, tumor suppressors, DNA repair, and last but not least, apoptosis-related genes through several mechanisms, such as point mutations, deletions, translocations and gene recombination. Moreover, implication of different tumorgenic signal transduction pathways, such as PI3K/AKT, STAT3, ERK1/2 and COX-2 in tobacco-induced tumorgenesis should not be underestimated. Conclusions: Although many facts about the carcinogenic character of tobacco are yet unknown, understanding the molecular mechanisms of cancer development associated with smoking could be promising for early detection, treatment, and reducing metastasis of tobacco-related cancers.

The Role and Function of Ras-association domain family in Cancer: A Review

“…This protein is involved in various signaling pathways which can induce apoptosis through Ras activation. It also acts independently of Ras and suppresses Akt signaling pathway through different mechanisms 1, 38, 84…”

“…This protein, like RASSF1A, can form Ras complex along with MOAP-1 protein active Bax. In melanoma cells, this protein can amplify the relationship between MST1 suppression kinase and B-Raf mutation, and suppress the mitogen-activated kinase protein (MAPK) pathway 9, 84. Note that RASSF6 has various mechanisms which can use Ras for tumor suppression.…”

Cancer Prevalence in E-Cigarette Users: A Retrospective Cross-Sectional NHANES Study

“…Polycyclic aromatic hydrocarbons (PAHs), nicotine and nicotine-derived nitrosamine ketone (NNK) play major roles in the pathogenesis of a wide range of cancers. These carcinogens can cause point mutations, deletions, translocations, and gene recombination and alter the expression of oncogenes, DNA repair, tumor suppressors, and apoptosis-related genes through several mechanisms [ 16 ]. Although the concentration of aerosol delivered by e-cigarettes is lower than traditional smoking, this does not render it harmless [ 17 ].…”

Effect of Conjugated Linoleic Acid (CLA) Supplementation on Expression of B-Cell Lymphoma-2 (Bcl-2) in the Bladder Epithelium of Wistar (Rattus norvegicus) Rats Exposed to Cigarette Smoke

“…The isomer of CLA significantly increased lipolysis in adipose, reduced fatty acid synthesis, and inhibited the expression of genes involved in the differentiation of pre-adipose to mature adipose to facilitate the process of lipogenesis ( 11 ). The effect of CLA on lipid and glucose metabolism is mediated by activation and inhibition of PPARs, particularly PPARγ ( 3 , 5 ), a transcription factor in the nucleus that has a vital role in fatty acid catabolism and storage. PPARα and PPARβ are involved in the expression of proteins essential for fatty acid oxidation, and PPARγ was involved in adipose differentiation.…”

“…PI3K/AKT which will increase the expression of Bcl-2 so that cell proliferation occurs. The expression of Bcl-2 can be suppressed in the presence of CLA ( 3 ).…”