Abstract
The following study characterizes at a molecular level the effects of boric acid on growth inhibition in the DU-145 human prostate cancer cell line. DU-145 prostate cancer cell growth has previously been reported to be completely inhibited when cultured in RPMI1640 media supplemented with 10% FBS and 25 mM Hepes in the presence of 1 mM boric acid. The complete growth inhibition was continuous in the presence of 1 mM boric acid, yet appeared to be only cytostatic in attached cells since removing boric acid resulted in resumption of growth at a normal rate. Lower doses (0.4 mM and 0.8 mM) of boric acid were also able to partially inhibit growth in attached cells in a dose dependent manner. In the current study clonogenic survival assays indicated that boric acid was able to kill DU-145 cells following a three-day exposure in a dose dependent manner. Flow cytometric analysis of DU-145 cells indicated that boric acid caused a block in the S-phase of the cell cycle (49%) compared to control cells (35%). Boric acid also induced apoptosis in detached cells in a dose dependent manner. Apoptosis was confirmed in treated cells using annenxin V and with fluorescent microscopy using Hoescht 3342 dye. An in vitro caspase 3 assay demonstrated that boric acid activated a mitochondrial apoptotic pathway in the DU-145 cell line. The results indicate that boric acid is capable of inducing apoptosis in a human prostate cancer cell line. Further study may lead to clinical applications for boric acid relevant to prostate cancer prevention and treatment.
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