Suppression activity of pro-apoptotic gene products in cancer cells, a potential application for cancer gene therapy

Overexpression of anti-apoptotic Bcl-2 and Bcl-X-L proteins may play a role in the development of resistance to cancer therapy. We examined the expres sion of these proteins in prostate, breast, and ovarian cancer cells. We fo und that some of these cancer cell lines expressed high levels of Bcl-X-L o r Bcl-2., In order to develop an effective strategy to overcome the potenti al inhibition of cancer therapy by Bcl-2 and Bcl-X-L, we tested the inhibit ory ability of several pro-apoptotic or tumor suppressor genes in these cel ls. The expression of these genes induced apoptosis or suppressed cell grow th with variable efficiency in these cells. Harakiri (Hrk) appears to resul t in the greatest induction of apoptosis or inhibition of cell growth. Mtd, bar and bcl-X-S were also effective in inhibiting cell growth. Furthermore e, transfection of Hrk, bar, or Mtd into these cells caused significantly less colony formation than in cells transfected with p53 or BRCA1. Therefor e, these results suggest that Hrk, bas and Mtd are potent therapeutic agent s for cancers expressing high levels of Bcl-2 and Bcl-X-L.