期刊
TOXICOLOGY MECHANISMS AND METHODS
卷 27, 期 1, 页码 1-17出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/15376516.2016.1268228
关键词
Polycyclic aromatic hydrocarbons; human carcinogenesis; cytochrome P450; aryl hydrocarbon receptor; DNA damage; reactive oxygen species; apoptosis
类别
资金
- Rapid Grant for Young Investigators (RGYI), India [BT/PR1/5090/GBD/27/309/2011]
- Department of Biotechnology, Science and Engineering Research Board (SERB), India [SR/SO/BB-0101/2012]
- Council of Scientific and Industrial Research (CSIR) [37 (1608)/13/EMR-II]
- Human Resource Development Group, Government of India
- CSIR
Polycyclic aromatic hydrocarbons (PAHs) comprise the major class of cancer-causing chemicals and are ranked ninth among the chemical compounds threatening to humans. Moreover, interest in PAHs has been mainly due to their genotoxic, teratogenic, mutagenic and carcinogenic property. Polymorphism in cytochrome P450 (CYP450) and aryl hydrocarbon receptor (AhR) has the capacity to convert procarcinogens into carcinogens, which is an imperative factor contributing to individual susceptibility to cancer development. The carcinogenicity potential of PAHs is related to their ability to bind to DNA, thereby enhances DNA cross-linking, causing a series of disruptive effects which can result in tumor initiation. They induce cellular toxicity by regulating the generation of reactive oxygen species (ROS), which arbitrate apoptosis. Additionally, cellular toxicity-mediated apoptotic and autophagic cell death and immune suppression by industrial pollutants PAH, provide fertile ground for the proliferation of mutated cells, which results in cancer growth and progression. PAHs play a foremost role in angiogenesis necessary for tumor metastasization by promoting the upregulation of metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF) and hypoxia inducible factor (HIF) in human cancer cells. This review sheds light on the molecular mechanisms of PAHs induced cancer development as well as autophagic and apoptotic cell death. Besides that authors have unraveled how phytotherapeutics is an alternate potential therapeutics acting as a savior from the toxic effects of PAHs for safer and cost effective perspectives.
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