Treatment of cancer using organoarsenicals
The subject invention provides organoarsenicals or salts thereof, compositions comprising an organoarsenical or a salt thereof, and methods of using the organoarsenicals or salts thereof, or compositions for inhibiting glutaminase and for treating cancers. Specifically, the subject invention provides methods of inhibiting glutaminase (e.g., KGA) catalytic activity in a cell, methods of treating cancer or a tumor via, for example, the inhibition of glutaminase activity, and methods of disrupting and/or inhibiting growth and proliferation of cancerous or tumorous cells.
1. A method of inhibiting kidney-type glutaminase (KGA) activity in a cell that expresses KGA, comprising contacting the cell with a trivalent organoarsenical, or a salt thereof, wherein the trivalent organoarsenical is trivalent hydroxyarsinothricin or trivalent roxarsone.
2. The method of claim 1 , the cell being a cancer cell.
3. The method of claim 2 , the cancer cell being a breast cancer cell.
4. The method of claim 3 , the breast cancer cell being a TNBC cell.
5. A method of treating triple-negative breast cancer (TNBC), the method comprising administering to a subject having TNBC an effective amount of a composition comprising a trivalent organoarsenical, and a pharmaceutically-acceptable carrier, the trivalent organoarsenical being trivalent hydroxyarsinothricin or trivalent roxarsone.
6. The method of claim 5 , the administration being through a local, oral, nasal, topical, intratumoural, transdermal, intra-articular, intravenous, intraperitoneal, intradermal, subcutaneous, or intramuscular route.
7. The method of claim 5 , further comprising evaluating the catalytic activity of KGA in TNBC cells of the subject.
8. A method of disrupting and/or inhibiting growth and proliferation of TNBC cells, the method comprising administering to a subject having TNBC an effective amount of a trivalent organoarsenical, the trivalent organoarsenical being trivalent hydroxyarsinothricin or trivalent roxarsone.
9. The method of claim 8 , further comprising detecting the catalytic activity of KGA in TNBC cells of the subject.