Arsenic in cancer therapy.
Arsenic, a natural substance that has been used as a drug for over 2000 years, has been revived because of its remarkable therapeutic efficacy in patients with acute promyelocytic leukemia (APL). Arsenic exerts a dose-dependent dual effect: it causes differentiation at low concentrations and apoptosis at relatively high concentrations. Specific degradation of the leukemogenic PML-RARalpha fusion protein induced by arsenic leads to the differentiation of leukemia cells. The arsenic-induced apoptosis occurs through direct effects on mitochondria, causing the release of apoptotic proteins into the cytosol and the activation of caspases. Preliminary in vitro studies have also extended the potential anti-cancer effect of arsenic to non-APL leukemias, lymphoid malignancies and other cancers. In vitro and in vivo studies demonstrate that arsenic exerts a broad spectrum of anti-cancer effects by induction of apoptosis, inhibition of cell proliferation, anti-angiogenesis and possible immunomodulation. Phase I and II clinical trials are underway to evaluate the feasibility, safety and potential effect of arsenic in various cancer types.
Hu
Jiong
J
Department of Hematology, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Second Medical University, Shanghai, China.
Fang
Jing
J
Dong
Yin
Y
Chen
Sai Juan
SJ
Chen
Zhu
Z
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001152:Arsenicals / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007938:Leukemia / Q000188:drug therapy; D008223:Lymphoma / Q000188:drug therapy; D009101:Multiple Myeloma / Q000188:drug therapy
D000970:Antineoplastic Agents; D001152:Arsenicals