Exploiting IR-Inducible NQ01 Levels Using B-Lapachone, A Novel Apoptotic Agent
Abstract
We theorize that Beta-lapachone is an effective agent against prostate cancer (CaP) cells/tumors. It kills cells by targeting elevated NQ01 levels in CaP tissue. Beta-Lapachone targets ionizing radiation (IR)-inducible NQ01. Normal cells with little or no NQ01 levels are spared, while IR-treated CaP cells expressing NQ01 are killed by apoptosis. Beta-Lapachone killing of CaP tumors is independent of p53, pRb, cell cycle status, or hormone (non)responsiveness and involves calpain activation. We are testing this theory using NQ01-deficient LNCaP cells, and comparing these cells to constitutively expressing NQ01 cells, with or without inhibitors of the enzyme (i.e., dicoumarol) . We are examining whether constitutive or inducible NQ01 levels are required for radiosensitization by Beta-lapachone. In Aim 1, in vitro responses and mechanisms of cell death after Beta-lapachone are examined, with or without IR, using cultured human CaP cells. In Aim #2, we will examine the efficacy of radiosensitization by Beta-lapachone in vivo using human CaP xenografts in male nude mice. Preclinical animal studies to move Beta-lapachone, from the bench to clinical trials against CaP have started.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2002
- Accession Number
- ADA405451
Entities
People
- David A. Boothman
Organizations
- Case Western Reserve University