The paradox of arsenic: molecular mechanisms of cell transformation and chemotherapeutic effects.
Arsenic is a well-documented carcinogen that also appears to be a valuable therapeutic tool in cancer treatment. This creates a paradox for which no unified hypothesis has been reached regarding the molecular mechanisms that determine whether arsenic will act as a carcinogen or as an effectual chemotherapeutic agent. Much of our knowledge with respect to the actions of arsenic has been drawn from epidemiological or clinical studies. The actions of arsenic are likely to be related to cell type, arsenic species, and length and dose of exposure. Arsenic unquestionably induces apoptosis and may specifically target certain tumor cells. Research data strongly suggest that arsenic influences distinct signaling pathways involved in mediating proliferation or apoptosis, including mitogen-activated protein kinases, p53, activator protein-1 or nuclear factor kappa B. The primary purpose of this review is to examine recent findings, from this laboratory and others, that focus on the molecular mechanisms of arsenic's actions in cell transformation and as a therapeutic agent.
Bode
Ann M
AM
The Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912, USA.
Dong
Zigang
Z
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001151:Arsenic / Q000009:adverse effects / Q000494:pharmacology*; D001152:Arsenicals / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced*; D005978:Glutathione / Q000502:physiology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D016328:NF-kappa B / Q000502:physiology; D009369:Neoplasms / Q000139:chemically induced* / Q000188:drug therapy; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy; D018808:Transcription Factor AP-1 / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects
D000970:Antineoplastic Agents; D001152:Arsenicals; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D005978:Glutathione; D001151:Arsenic