Calcitriol e colecalciferol aumentam a diferenciação e a apoptose em células do
osteosarcoma humano
Effect of 25-hydroxyvitamin D3 and 1 α,25 dihydroxyvitamin D3
on differentiation and apoptosis of human osteosarcoma cell
lines.
Thompson L1, Wang S, Tawfik O, Templeton K, Tancabelic J, Pinson D, Anderson HC, Keighley
J, Garimella R.
J Orthop Res. 2012 May;30(5):831-44. doi: 10.1002/jor.21585. Epub 2011 Oct 31.
Author information

1
Department of Dietetics and Nutrition, University of Kansas Medical Center, Kansas
City, Kansas, USA.
Abstract
Osteosarcoma (OS) is a malignant bone tumor predominantly affecting children and
adolescents. OS has a 60% survival rate with current treatments; hence, there is a need to
identify novel adjuncts to chemotherapeutic regimens. In this pilot study, we investigated the
dose-response to 1α,25-dihdroxyvitamin D(3) (1,α 25(OH)(2) D(3)) and 25-hydroxyvitamin D(3)
(25(OH)D(3)) by human OS cell lines, SaOS-2, and 143B. We hypothesized that 1,α 25(OH)(2)
D(3) and 25(OH)D(3) would stimulate differentiation and induce apoptosis in OS cells in a dosedependent manner. Human OS cell lines, SaOS-2, and 143B, were treated with 1,α
25(OH)(2)D(3) or 25(OH)D(3) or an ethanol control, respectively, at concentrations ranging from
1 to 1,000 nM. Ki67 (a marker of cellular proliferation) immunocytochemistry revealed no
significant changes in the expression of Ki-67 or MIB-1 in 1α,25(OH)(2)D(3) or 25(OH)D(3)
treated SaOS-2 or 143B cells. Both control and 1α,25(OH)(2) D(3) treated SaOS-2 and 143B
cells expressed vitamin D receptor (VDR). Markers of osteoblastic differentiation in 143B cells
and SaOS-2 cells were induced by both 25(OH)D(3) and 1α,25(OH)(2) D, and evident by
increases in alkaline phosphatase (ALP) activity, osteocalcin (OCN) mRNA expression, and
mineralization of extra-cellular matrix (ECM) by alizarin red staining. An increasing trend in
apoptosis in response to 25(OH)D(3), in both SaOS-2 and 143B cells was detected by terminal
deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining. With
1α,25(OH)(2)D(3) treatment, apoptosis was evident at higher concentrations only. These
preliminary findings suggest that OS cells express VDR and respond to 25(OH)D(3) and
1α,25(OH)(2)D(3) by undergoing differentiation and apoptosis.
Copyright © 2011 Orthopaedic Research Society.
Comment in

Heterogeneity in osteosarcoma cell lines and the biological effects of the chemical
structure of 25-hydroxyvitamin D₃ and 1 a,25 dihydroxyvitamin D₃. [J Orthop Res. 2012]
PMID:22042758