Immunomodulating tellurium compounds as anti-cancer agents.
Tellurium is a rare element, which has been regarded as a toxic, non-essential trace element; its biological role, if any, has not been clearly established to date. The investigation of therapeutic activities of tellurium compounds is rather limited in the literature, despite the relative abundance of tellurium in the human body. Nevertheless, the varied activities of tellurium agents in both malignant and normal cells are extremely exciting, though very complex. Not surprisingly, an increased interest in tellurium among biological chemists and pharmacists has fuelled the search for more and more diverse tellurium compounds. The present review will focus on two small inorganic tellurium complexes, ammonium trichloro(dioxoethylene-O,O')tellurate (AS101) and Octa-O-bis-(R,R)-tartarate ditellurane (SAS), thoroughly investigated by us, converging at their anti-cancer properties, and elucidating their mechanism of action. AS101 is probably the most extensively studied synthetic tellurium compound from the standpoint of its biological activity. It is a potent immunomodulator (both in vitro and in vivo) with a variety of potential therapeutic applications. It is probably the only tellurium compound to be tested in phase I/II clinical studies in cancer patients. The effects of AS101 and SAS are primarily caused by their specific Te(IV) redox-modulating activities enabling the inactivation of cysteine proteases such as cathepsin B, inhibition of specific tumor survival proteins like survivin, or obstruction of tumor IL-10 production. All of these have profound consequences regarding anti-tumor activity or sensitization of tumors to chemotherapy. These properties, coupled with the excellent safety profile of the compounds, suggest promising anti-cancer therapeutic potential for tellurium compounds such as AS101 or SAS.
The Safdié Institute for AIDS and Immunology Research, The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel. srednib@mail.biu.ac.il
Benjamin
B
Sredni
D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D004285:Dogs; D005030:Ethylenes / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007155:Immunologic Factors / Q000502:physiology; D056747:Immunomodulation / Q000502:physiology; D016753:Interleukin-10 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy*; D009942:Organometallic Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D013644:Tartrates / Q000494:pharmacology / Q000627:therapeutic use*
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D015853:Cysteine Proteinase Inhibitors; D005030:Ethylenes; D007155:Immunologic Factors; D009942:Organometallic Compounds; D013644:Tartrates; C530751:octa-O-bistartarate ditellurane; D016753:Interleukin-10; C054105:ammonium trichloro(dioxoethylene-O,O'-)tellurate