1alpha,25-dihydroxyvitamin D(3) (calcitriol) and its analogue,
19-nor-1alpha,25(OH)(2)D(2), potentiate the effects of ionising
radiation on human prostate cancer cells.
Br J Cancer. 2003 Aug 18;89(4):746-53.
of Radiation Oncology, Comprehensive Cancer Center of Wake Forest
University School of Medicine, Winston-Salem, NC 27157, USA.
with external beam radiation or brachytherapy is an established
therapeutic modality for prostate cancer. Approximately 30% of patients
with localised prostate cancer relapse at the irradiated site.
Secondary effects of ionising radiation (IR), for example, bowel and
bladder complications, are common. Thus, the search for biological
response modifiers that could potentiate the therapeutic effects of
radiation and limit the occurrence of serious side effects is an
important task in prostate cancer therapy. 1alpha,25-Dihydroxyvitamin
D(3) (calcitriol), the active metabolite of vitamin D, and its
analogues are under investigation for the treatment of several
malignancies including prostate cancer.
Here, we report that
1alpha,25-dihydroxyvitamin D(3) and its less calcaemic analogue
19-nor-1alpha,25-(OH)(2)D(2) (Zemplar) act synergistically with IR to
inhibit the growth of the human prostate cancer cells in vitro.
1alpha,25-dihydroxyvitamin D(3) potentiated IR-induced apoptosis of
LNCaP cells, and nanomolar doses of 1alpha,25-dihydroxyvitamin D(3) and
19-nor-1alpha,25-(OH)(2)D(2) showed synergistic inhibition of growth of
LNCaP cells at radiobiologically relevant doses of IR (1-2 Gy). At
higher doses of IR, the combination of 1alpha,25-dihydroxyvitamin D(3)
and IR or 19-nor-1alpha,25-(OH)(2)D(2) and IR resulted in moderate
antagonism. The synergistic effect at radiobiologically relevant doses
of radiation suggests that a combination of 1alpha,25-dihydroxyvitamin
D(3) or 19-nor-1alpha,25-(OH)(2)D(2) with IR could permit a reduction
in the dose of radiation given clinically and thus potentially reduce