Calcitriol-induced apoptosis in LNCaP cells is blocked by overexpression of Bcl-2.
While the role of vitamin D in bone and mineral metabolism has been investigated extensively, the role of the vitamin D receptor in other tissues is less well understood. 1,25-Dihydroxyvitamin D3 (calcitriol) can act as a differentiating agent in normal tissues and can inhibit the growth of many cancer cell lines including LNCaP prostate cancer cells. We have shown previously that calcitriol causes LNCaP cell accumulation in the G0/G1 phase of the cell cycle. In this study, we demonstrate that calcitriol also induces apoptosis of LNCaP cells. The calcitriol-induced apoptosis is accompanied by a down-regulation of Bcl-2 and Bcl-X(L) proteins, both of which protect cells from undergoing apoptosis. Other proteins important in apoptotic control, Bax, Mcl-1, and Bcl-X(S), are unaffected by calcitriol treatment. We find that overexpression of Bcl-2 blocks calcitriol-induced apoptosis and reduces, but does not eliminate, calcitriol-induced growth inhibition. We conclude that both regulation of cell cycle and the apoptotic pathway are involved in calcitriol action in prostate cancer cells.
Blutt
S E
SE
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
McDonnell
T J
TJ
Polek
T C
TC
Weigel
N L
NL
D017209:Apoptosis; D015153:Blotting, Western; D002117:Calcitriol / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D005434:Flow Cytometry; D019085:Fluorescent Antibody Technique, Direct; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis; D011471:Prostatic Neoplasms; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured
D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D002117:Calcitriol