Metabolism and the Paradoxical Effects of Arsenic: Carcinogenesis and Anticancer

Xing      Cui; Yayoi      Kobayashi; Makoto      Akashi; Ryuichi      Okayasu

Abstract

Arsenic, a known human carcinogen, can induce tumors of the skin, urinary bladder, liver and lung etc.. On the other hand, arsenic is also a novel promising anticancer agent, and can be used effectively to treat acute promyelocytic leukemia (APL) and some other tumors. These paradoxical effects of arsenic not only result from direct or indirect influences on the genetic and epigenetic levels, but are also closely correlated with unique arsenic metabolism. This article reviews our recent studies as well as other reports on arsenic metabolism and epigenetic changes of DNA methylation during its metabolism. We also summarize the clinical use of arsenic trioxide (As2O3) to date and discuss new therapeutic strategies such as concurrent arsenic-radiation therapy to achieve local tumor control and enhance the radiosensitivity of solid tumors.

Keywords: Carcinogenesis, tumors, anticancer agent, acute promyelocytic leukemia (APL), arsenic metabolism, arsenic-radiation therapy, urinary bladder, Arsenic Toxicity