| ironjustice@aol.com 2005-10-06, 10:48 pm |
| Gynecol Oncol. 2005 Sep 30; [Epub ahead of print] Links
Iron chelators deferoxamine and diethylenetriamine pentaacetic acid
induce apoptosis in ovarian carcinoma.
Brard L, Granai CO, Swamy N.
Program in Women's Oncology, Department of Obstetrics and Gynecology,
Women and Infants' Hospital, Brown University, Providence, RI 02905,
USA.
OBJECTIVES.: Ovarian cancer remains a leading cause of death in women
and development of new therapies is essential. Deprivation of iron
(Fe), an essential micro-nutrient, by chelation is known to inhibit
proliferation of several human cancers but its potential in ovarian
cancer treatment remains unknown. We have evaluated the
anti-proliferative activities of iron chelators, deferoxamine (DFO),
and diethylenetriamine pentaacetic acid (DTPA), in human and rat
ovarian cancer cells. METHODS.: The effect of DFO and DTPA on CaOV-3
(human) and NUTU-19 (rat) ovarian cancer cells was determined by cell
proliferation and apoptosis assays (Hoechst staining, DNA
fragmentation, and caspase activation), cell cycle analysis, and Fe
supplementation studies. RESULTS.: DFO and DTPA were cytotoxic to
ovarian cancer cells in a dose- and time-dependent manner. DFO
inhibited proliferation of NUTU-19 and CaOV-3 cells (IC(50) at 45 and
280 muM, respectively), while DTPA inhibited proliferation of only
NUTU-19 cells (IC(50) at 50 muM), at 48 h. DNA synthesis was inhibited
in CaOV-3 cells by DFO (>90% at 200 muM) and in NUTU-19 by both DFO and
DTPA (>90% at 50 muM). Fe supplementation effectively reversed the
cytotoxic effects of DFO and DTPA. Cell cycle analysis showed a G0/G1-
and S-phase block with increased apoptosis. DNA fragmentation analysis
confirmed apoptosis. Increase in caspase-3, -8, and -9 activities (
approximately 2.4-fold) was associated with apoptosis. CONCLUSIONS.:
Our studies show that Fe chelators suppress ovarian cancer growth by
inhibiting proliferation and inducing apoptosis. Therefore, Fe
chelators can be potentially developed as novel therapeutic agents to
treat ovarian cancer.
PMID: 16203029 [PubMed - as supplied by publisher]
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