Arsenic and Its Combinations in Cancer Therapeutics

Abstract

Arsenic is a metalloid that is considered to be a paradox in terms of its role both as a carcinogen and as a therapeutic agent. Chronic exposure to arsenic in drinking water has been linked with the development of various pathological conditions including cancer. Nevertheless, the therapeutic potential of arsenic and its derivatives in a variety of diseases have been exploited in the past. However, its role and mechanism of action as a therapeutic agent still remain an active area of research and investigation. Our ongoing work also suggests varied responses in cancer cells exposed to lower versus higher concentrations of arsenic. Furthermore, the arsenic combinations with chemopreventive or anticancer agents have been observed to sensitize the cell for cell-cycle arrest and cell death. Here, we have provided the account of recent updates on the mechanism of action of arsenic and its derivatives that lead to various disorders, and its role as a therapeutic agent both as a single agent as well as in combination chemotherapy.

Arsenic in the human food chain, biotransformation and toxicology – Review focusing on seafood arsenic

“…The main reason for this is that As undergoes a number of complicated metabolic conversions in vivo, and its metabolites and As itself interacts with both intra-and extracellular macromolecules. There is also lack of appropriate animal models since rodents, which usually are the species used in toxicity studies, differ from humans regarding As metabolism [55].…”

“…Both As (III) and As (V) may bind to thiol groups and membrane lipids, resulting in inhibition of functional groups in enzymes and altered fluidity of membrane lipids, respectively [55]. Some…”

“…After absorption in the GI-tract, As is taken up in the bloodstream and distributed between the plasma and the erythrocytes where it is bound to hemoglobin and further transported into the cells by the aquaglyceroporins 3, 7 and 9, which are phosphate-and hexose permease transporters [11,55]. Animal studies have shown that after administration of iAs, it is distributed to all tissues, with high concentrations in the kidney, lung, urinary bladder, skin, blood and liver [56,57].…”

Silibinin Combination with Arsenic Strongly Inhibits Survival and Invasiveness of Human Prostate Carcinoma Cells

“…The prowess of arsenic as an anticancer agent has also been reported in other cancers both alone and in combination with phytochemicals and other chemotherapeutic drugs (21). However, clinical trials have FIG.…”

Speciation, Metabolism, Toxicity, and Protein-binding of Different Arsenic Species in Human Cells

“…20,21 The manner in which arsenic-containing compounds generate ROS and cellular oxidative stress is quite complex.…”