Center for Life Sciences, Vidyasagar University, Midnapore-721102, West Bengal, India; Post Graduate Department of Biochemistry and Biotechnology Cell and Molecular Therapeutics Laboratory, Oriental Institute of Science and Technology, Midnapore-721102, West Bengal, India.
Professor, Dept. of Zoology, Vidyasagar University, Midnapore, 721102, West Bengal, India; (on lien) Vice Chancellor, Mahatma Gandhi University, Purba Medinipur, 721628, West Bengal, India.
Ecotoxicol Environ Saf. 2021 Jan 15;208:111752. doi: 10.1016/j.ecoenv.2020.111752. Epub 2020 Dec 11.
Arsenic is a toxic heavy metal vastly dispersed all over the earth crust. It manifests several major adverse health issues to millions of arsenic exposed populations. Arsenic is associated with different types of cancer, cardiovascular disorders, diabetes, hypertension and many other diseases. On the contrary, arsenic (arsenic trioxide, AsO) is used as a chemotherapeutic agent in the treatment of acute promyelocytic leukemia. Balance between arsenic induced cellular proliferations and apoptosis finally decide the outcome of its transformation rate. Arsenic propagates signals via cellular and nuclear pathways depending upon the chemical nature, and metabolic-fates of the arsenical compounds. Arsenic toxicity is propagated via ROS induced stress to DNA-repair mechanism and mitochondrial stability in the cell. ROS induced alteration in p53 regulation and some mitogen/ oncogenic functions determine the transformation outcome influencing cyclin-cdk complexes. Growth factor regulator proteins such as c-Jun, c-fos and c-myc are influenced by chronic arsenic exposure. In this review we have delineated arsenic induced ROS regulations of epidermal growth factor receptor (EGFR), NF-ĸβ, MAP kinase, matrix-metalloproteinases (MMPs). The role of these signaling molecules has been discussed in relation to cellular apoptosis, cellular proliferation and neoplastic transformation. The arsenic stimulated pathways which help in proliferation and neoplastic transformation ultimately resulted in cancer manifestation whereas apoptotic pathways inhibited carcinogenesis. Therapeutic strategies against arsenic should be designed taking into account all these factors.
砷是一种广泛分布于地壳中的有毒重金属。它对数百万接触砷的人群的健康造成了多种严重的不良影响。砷与多种类型的癌症、心血管疾病、糖尿病、高血压和许多其他疾病有关。相反，砷（三氧化二砷，AsO）被用作治疗急性早幼粒细胞白血病的化疗药物。砷诱导的细胞增殖和凋亡之间的平衡最终决定了其转化率的结果。砷通过细胞和核途径传播信号，具体取决于砷化合物的化学性质和代谢命运。砷毒性通过 ROS 诱导的 DNA 修复机制和线粒体稳定性的应激在细胞中传播。ROS 诱导的 p53 调节和一些有丝分裂原/致癌功能的改变决定了影响细胞周期蛋白-CDK 复合物的转化结果。生长因子调节剂蛋白，如 c-Jun、c-fos 和 c-myc，受慢性砷暴露的影响。在这篇综述中，我们描述了砷诱导的 ROS 对表皮生长因子受体（EGFR）、NF-ĸβ、MAP 激酶、基质金属蛋白酶（MMPs）的调节作用。这些信号分子的作用与细胞凋亡、细胞增殖和肿瘤转化有关。最终导致癌症表现的砷刺激的增殖和肿瘤转化途径，而凋亡途径则抑制了致癌作用。针对砷的治疗策略应该考虑到所有这些因素。
