Dutasteride Induces Apoptosis In Androgen Sensitive Prostate Cancer Cell Lines

UroToday.com - Dr. McCrohan as research colleagues from University College Dublin report that the dual 5 a-reductase inhibitor dutasteride induces apoptosis in androgen sensitive, but not androgen insensitive prostate cancer (CaP) cell lines and primary cultures. Their work appears in the epub version of Cancer.

The administration of dutasteride (0.1-10mM) resulted in apoptosis in androgen sensitive LNCaP, pwR-1E, PNT-2 and PC3 (AR) cells. Apoptosis was assessed by quantification of cells with hypodiploid DNA by propidium iodide incorporation. LNCaP and PC3 (AR) cells remained responsive to treatment to 4 and 5 days, respectively. Androgen insensitive PC3 cells did not respond to dutasteride.

In first passage CaP primary cultures, dutasteride induced apoptosis in 7 samples, but not in 9 samples. The difference could not be explained by differences in dutasteride on cell cycle progression or expression of 5 a-reductase isoforms.

The Reduction by Dutasteride of Prostate Cancer Events study is testing dutasteride as chemoprevention and this basic science work adds to the understanding of dutasteride mechanism. It also provides rationale for use of dutasteride in combination with intermittent androgen deprivation therapy, now being tested in clinical trials.

By Christopher P. Evans, MD
Reference:
Cancer. 2006 Jun 15;106(12):2743-52
Link Here.
Maria McCrohan A, Morrissey C, O'keane C, Mulligan N, Watson C, Smith J, Fitzpatrick JM, Watson RW

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