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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.

Dunlap N, Schwartz GG, Eads D, Cramer SD, Sherk AB, John V, Koumenis C - Br. J. Cancer (2003)

Bottom Line: Radiotherapy with external beam radiation or brachytherapy is an established therapeutic modality for prostate cancer.Secondary effects of ionising radiation (IR), for example, bowel and bladder complications, are common.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiation Oncology, Comprehensive Cancer Center of Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.

ABSTRACT
Radiotherapy 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 treatment-related morbidity.

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Related in: MedlinePlus

Dose–response effects of 1α,25(OH)2D3 (A) or 19-nor-1α,25(OH)2D2 (B) alone, or combined with IR on the growth of LNCaP prostate tumour cells. Cells were plated in medium and drugs were added 24 h later. Cells were irradiated 24 h following addition of 1α,25(OH)2D3 or 19-nor-1α,25(OH)2D2 and allowed to grow for an additional 7 days, at which time MTT assay was performed as described in Materials and Methods. Optical density (OD) values represent the average of four readings per experiment. Each experiment was performed three times. Error bars represent s.e. values.
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fig2: Dose–response effects of 1α,25(OH)2D3 (A) or 19-nor-1α,25(OH)2D2 (B) alone, or combined with IR on the growth of LNCaP prostate tumour cells. Cells were plated in medium and drugs were added 24 h later. Cells were irradiated 24 h following addition of 1α,25(OH)2D3 or 19-nor-1α,25(OH)2D2 and allowed to grow for an additional 7 days, at which time MTT assay was performed as described in Materials and Methods. Optical density (OD) values represent the average of four readings per experiment. Each experiment was performed three times. Error bars represent s.e. values.

Mentions: While apoptotic assays can be useful in determining the short-term effects of agents on cells, they may not reflect the long-term effects of these agents on cellular proliferation. To investigate the effects of 1α,25(OH)2D3 and 19-nor-1α,25(OH)2D2 on long-term proliferation of prostate cells, we treated LNCaP cells with different doses of the hormones and IR, and assessed cell viability 8 days later using the MTT assay. As seen in Figure 2A and BFigure 2


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.

Dunlap N, Schwartz GG, Eads D, Cramer SD, Sherk AB, John V, Koumenis C - Br. J. Cancer (2003)

Dose–response effects of 1α,25(OH)2D3 (A) or 19-nor-1α,25(OH)2D2 (B) alone, or combined with IR on the growth of LNCaP prostate tumour cells. Cells were plated in medium and drugs were added 24 h later. Cells were irradiated 24 h following addition of 1α,25(OH)2D3 or 19-nor-1α,25(OH)2D2 and allowed to grow for an additional 7 days, at which time MTT assay was performed as described in Materials and Methods. Optical density (OD) values represent the average of four readings per experiment. Each experiment was performed three times. Error bars represent s.e. values.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2376931&req=5

fig2: Dose–response effects of 1α,25(OH)2D3 (A) or 19-nor-1α,25(OH)2D2 (B) alone, or combined with IR on the growth of LNCaP prostate tumour cells. Cells were plated in medium and drugs were added 24 h later. Cells were irradiated 24 h following addition of 1α,25(OH)2D3 or 19-nor-1α,25(OH)2D2 and allowed to grow for an additional 7 days, at which time MTT assay was performed as described in Materials and Methods. Optical density (OD) values represent the average of four readings per experiment. Each experiment was performed three times. Error bars represent s.e. values.
Mentions: While apoptotic assays can be useful in determining the short-term effects of agents on cells, they may not reflect the long-term effects of these agents on cellular proliferation. To investigate the effects of 1α,25(OH)2D3 and 19-nor-1α,25(OH)2D2 on long-term proliferation of prostate cells, we treated LNCaP cells with different doses of the hormones and IR, and assessed cell viability 8 days later using the MTT assay. As seen in Figure 2A and BFigure 2

Bottom Line: Radiotherapy with external beam radiation or brachytherapy is an established therapeutic modality for prostate cancer.Secondary effects of ionising radiation (IR), for example, bowel and bladder complications, are common.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiation Oncology, Comprehensive Cancer Center of Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.

ABSTRACT
Radiotherapy 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 treatment-related morbidity.

Show MeSH
Related in: MedlinePlus