Disruptive environmental chemicals and cellular mechanisms that confer resistance to cell death
Kannan Badri Narayanan1, Manaf Ali2, Barry J Barclay3
1Department of Chemistry and Biochemistry, Yeungnam University, Gyeongsan 712-749, South Korea, Sultan Zainal Abidin University, Malaysia, Plant Biotechnologies Inc, St. Albert AB, Canada, Computer Science Department, Southern Illinois University, Carbondale, IL 62901, USA, Department of Urology, University of California Davis, Sacramento, CA 95817, USA, Department of Pharmacology and Toxicology, University of Vienna, Austria, University of Puerto Rico, Medical Sciences Campus, School of Public Health, Nutrition Program, San Juan Puerto Rico 00936-5067, USA, Department of Anatomy, College of Medicine, Yeungnam University, Daegu, 705-717, South Korea, School of Biomedical Science, The Chinese University Of Hong Kong, Hong Kong, China, Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand, Department of Otolaryngology/Head and Neck Surgery, Head and Neck Cancer Research Division, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA, Department of Pharmaceutical Sciences, Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV 26506, USA, Department of Molecular Medicine and Medical Biotechnology, Federico II University of Naples, 80131 Naples, Italy, Department of Molecular and Experimental Medicine, MEM 180, The Scripps Research Institute, La Jolla, CA 92037, USA, Department of Biology, Jackson State University, Jackson, MS 39217, USA, Department of Pathology, Kuwait University, Safat 13110, Kuwait, Department of Experimental and Clinical Medicine, University of Firenze, Firenze, 50134, Italy, Department of Environmental and Radiological Health Sciences, Colorado state University/ Colorado School of Public Health, Fort Collins, CO 80523-1680, USA, Center for Environmental Carcinogenesis and Risk Assessment, Environmental Protection and Health Prevention Agency, Bologna, 40126, Italy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Se
Abstract:
Cell death is a process of dying within biological cells that are ceasing to function. This process is essential in regulating organism development, tissue homeostasis, and to eliminate cells in the body that are irreparably damaged. In general, dysfunction in normal cellular death is tightly linked to cancer progression. Specifically, the up-regulation of pro-survival factors, including oncogenic factors and antiapoptotic signaling pathways, and the down-regulation of pro-apoptotic factors, including tumor suppressive factors, confers resistance to cell death in tumor cells, which supports the emergence of a fully immortalized cellular phenotype. This review considers the potential relevance of ubiquitous environmental chemical exposures that have been shown to disrupt key pathways and mechanisms associated with this sort of dysfunction. Specifically, bisphenol A, chlorothalonil, dibutyl phthalate, dichlorvos, lindane, linuron, methoxychlor and oxyfluorfen are discussed as prototypical chemical disruptors; as their effects relate to resistance to cell death, as constituents within environmental mixtures and as potential contributors to environmental carcinogenesis.
Insights
Environmental chemicals disrupt cell death pathways, promoting cancer. This review examines how substances like BPA and phthalates contribute to cell death resistance and carcinogenesis.
Area of Science:
- Cell Biology
- Toxicology
- Environmental Health
Background:
- Cell death is crucial for development and tissue health.
- Dysfunctional cell death is linked to cancer progression.
- Tumor cells resist death via altered survival and apoptotic signaling.
Purpose of the Study:
- To review environmental chemical exposures that disrupt cell death.
- To examine specific chemical disruptors and their mechanisms.
- To assess their role in environmental carcinogenesis.
Main Methods:
- Literature review of environmental chemical impacts on cell death pathways.
- Analysis of specific chemicals: bisphenol A, chlorothalonil, dibutyl phthalate, dichlorvos, lindane, linuron, methoxychlor, oxyfluorfen.
- Evaluation of their role in cell death resistance and carcinogenesis.
Main Results:
- Ubiquitous environmental chemicals can disrupt cell death mechanisms.
- These disruptors promote pro-survival and anti-apoptotic signaling.
- They contribute to resistance to cell death in tumor cells.
Conclusions:
- Environmental chemical exposures are potential contributors to cancer.
- Understanding these disruptors is key to addressing environmental carcinogenesis.
- Targeting cell death pathways affected by chemicals may offer therapeutic strategies.
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