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Vitamin D3 stimulates embryonic stem cells but inhibits migration and growth of ovarian cancer and teratocarcinoma cell lines.

Abdelbaset-Ismail A, Pedziwiatr D, Suszyńska E, Sluczanowska-Glabowska S, Schneider G, Kakar SS, Ratajczak MZ - J Ovarian Res (2016)

Bottom Line: We evaluated expression of Vitamin D3 receptor (VDR) in these cells as well as effect of vitamin D3 exposure on cell proliferation and migration.We also found that the ESD3 murine immortalized embryonic stem cell line and normal, pluripotent, germline-marker-positive very small embryonic-like stem cells (VSELs) isolated from adult tissues are stimulated by vitamin D3, which suggests that vitamin D3 affects the earliest stages of embryogenesis.We found that however all normal and malignant germ-line derived cells express functional VDR, Vitamin D3 differently affects their proliferation and migration.

View Article: PubMed Central - PubMed

Affiliation: Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, 500 S. Floyd Street, Rm. 107, Louisville, KY, 40202, USA.

ABSTRACT

Background: Deficiency in Vitamin D3 (cholecalciferol) may predispose to some malignancies, including gonadal tumors and in experimental models vitamin D3 has been proven to inhibit the growth of cancer cells. To learn more about the potential role of vitamin D3 in cancerogenesis, we evaluated the expression and functionality of the vitamin D receptor (VDR) and its role in metastasis of ovarian cancer cells and of murine and human teratocarcinoma cell lines.

Methods: In our studies we employed murine embrynic stem cells (ESD3), murine (P19) and human (NTERA-2) teratocarcimona cells lines, human ovarian cancer cells (A2780) as well as purified murine and human purified very small embryonic like stem cells (VSELs). We evaluated expression of Vitamin D3 receptor (VDR) in these cells as well as effect of vitamin D3 exposure on cell proliferation and migration.

Results: We here provide also more evidence for the role of vitamin D3 in germline-derived malignancies, and this evidence supports the proposal that vitamin D3 treatment inhibits growth and metastatic potential of several germline-derived malignancies. We also found that the ESD3 murine immortalized embryonic stem cell line and normal, pluripotent, germline-marker-positive very small embryonic-like stem cells (VSELs) isolated from adult tissues are stimulated by vitamin D3, which suggests that vitamin D3 affects the earliest stages of embryogenesis.

Conclusions: We found that however all normal and malignant germ-line derived cells express functional VDR, Vitamin D3 differently affects their proliferation and migration. We postulate that while Vitamin D3 as anticancer drug inhibits proliferation of malignant cells, it may protect normal stem cells that play an important role in development and tissue/organ regeneration.

No MeSH data available.


Related in: MedlinePlus

1,25-dihydroxyvitamin D3 induces apoptosis of human ovarian cancer cells in vitro. Panel a The A2780 human ovarian cancer cell line was treated with 1,25-dihydroxyvitamin D3 at concentrations ranging from 10−10–10−8 M for 16 h, and apoptosis was detected using the AnnexinV–FITC apoptosis kit and analyzed using flow cytometry. The data shown here indicate the induction of significant early apoptosis in cells treated with 10−9 M 1,25-dihydroxyvitamin D3 compared with cells treated with vehicle only. In this experiment, 10 % DMSO was used as positive control. The means of two experiments in triplicate were used. For statistical comparisons, a one-way analysis of variance and a Tukey’s test for post hoc analysis were carried out, and means ± SD are shown. Significance level: *p ≤ 0.05 versus control (untreated) cells. Panel b In parallel, treatment of the A2780 human ovarian cancer cell line with 1,25-dihydroxyvitamin D3 led to inhibition of phosphorylation of the p42/44 MAPK and AKTser473 intracellular pathway proteins in dose-dependent responses. Human ovarian cancer cells (2 × 106 cells/mL) were incubated for 12 h in RPMI with 0.5 % BSA culture medium containing either 1,25-dihydroxyvitamin D3 at various concentrations (10−10–10−8 M) or vehicle only. The experiment was carried out twice with similar results, and representative blots are shown
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Fig3: 1,25-dihydroxyvitamin D3 induces apoptosis of human ovarian cancer cells in vitro. Panel a The A2780 human ovarian cancer cell line was treated with 1,25-dihydroxyvitamin D3 at concentrations ranging from 10−10–10−8 M for 16 h, and apoptosis was detected using the AnnexinV–FITC apoptosis kit and analyzed using flow cytometry. The data shown here indicate the induction of significant early apoptosis in cells treated with 10−9 M 1,25-dihydroxyvitamin D3 compared with cells treated with vehicle only. In this experiment, 10 % DMSO was used as positive control. The means of two experiments in triplicate were used. For statistical comparisons, a one-way analysis of variance and a Tukey’s test for post hoc analysis were carried out, and means ± SD are shown. Significance level: *p ≤ 0.05 versus control (untreated) cells. Panel b In parallel, treatment of the A2780 human ovarian cancer cell line with 1,25-dihydroxyvitamin D3 led to inhibition of phosphorylation of the p42/44 MAPK and AKTser473 intracellular pathway proteins in dose-dependent responses. Human ovarian cancer cells (2 × 106 cells/mL) were incubated for 12 h in RPMI with 0.5 % BSA culture medium containing either 1,25-dihydroxyvitamin D3 at various concentrations (10−10–10−8 M) or vehicle only. The experiment was carried out twice with similar results, and representative blots are shown

Mentions: These changes in migration and adhesion can be explained by the pro-apoptotic effects of increasing doses of vitamin D3 (Fig. 3). As shown in Fig. 3, panel a, exposure of the A2780 ovarian cancer cell line to vitamin D3 resulted in an increase in the number of early and late apoptotic cells, which correlated with impaired vitamin D3 signaling in these cells (Fig. 3, panel b).Fig. 3


Vitamin D3 stimulates embryonic stem cells but inhibits migration and growth of ovarian cancer and teratocarcinoma cell lines.

Abdelbaset-Ismail A, Pedziwiatr D, Suszyńska E, Sluczanowska-Glabowska S, Schneider G, Kakar SS, Ratajczak MZ - J Ovarian Res (2016)

1,25-dihydroxyvitamin D3 induces apoptosis of human ovarian cancer cells in vitro. Panel a The A2780 human ovarian cancer cell line was treated with 1,25-dihydroxyvitamin D3 at concentrations ranging from 10−10–10−8 M for 16 h, and apoptosis was detected using the AnnexinV–FITC apoptosis kit and analyzed using flow cytometry. The data shown here indicate the induction of significant early apoptosis in cells treated with 10−9 M 1,25-dihydroxyvitamin D3 compared with cells treated with vehicle only. In this experiment, 10 % DMSO was used as positive control. The means of two experiments in triplicate were used. For statistical comparisons, a one-way analysis of variance and a Tukey’s test for post hoc analysis were carried out, and means ± SD are shown. Significance level: *p ≤ 0.05 versus control (untreated) cells. Panel b In parallel, treatment of the A2780 human ovarian cancer cell line with 1,25-dihydroxyvitamin D3 led to inhibition of phosphorylation of the p42/44 MAPK and AKTser473 intracellular pathway proteins in dose-dependent responses. Human ovarian cancer cells (2 × 106 cells/mL) were incubated for 12 h in RPMI with 0.5 % BSA culture medium containing either 1,25-dihydroxyvitamin D3 at various concentrations (10−10–10−8 M) or vehicle only. The experiment was carried out twice with similar results, and representative blots are shown
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4835879&req=5

Fig3: 1,25-dihydroxyvitamin D3 induces apoptosis of human ovarian cancer cells in vitro. Panel a The A2780 human ovarian cancer cell line was treated with 1,25-dihydroxyvitamin D3 at concentrations ranging from 10−10–10−8 M for 16 h, and apoptosis was detected using the AnnexinV–FITC apoptosis kit and analyzed using flow cytometry. The data shown here indicate the induction of significant early apoptosis in cells treated with 10−9 M 1,25-dihydroxyvitamin D3 compared with cells treated with vehicle only. In this experiment, 10 % DMSO was used as positive control. The means of two experiments in triplicate were used. For statistical comparisons, a one-way analysis of variance and a Tukey’s test for post hoc analysis were carried out, and means ± SD are shown. Significance level: *p ≤ 0.05 versus control (untreated) cells. Panel b In parallel, treatment of the A2780 human ovarian cancer cell line with 1,25-dihydroxyvitamin D3 led to inhibition of phosphorylation of the p42/44 MAPK and AKTser473 intracellular pathway proteins in dose-dependent responses. Human ovarian cancer cells (2 × 106 cells/mL) were incubated for 12 h in RPMI with 0.5 % BSA culture medium containing either 1,25-dihydroxyvitamin D3 at various concentrations (10−10–10−8 M) or vehicle only. The experiment was carried out twice with similar results, and representative blots are shown
Mentions: These changes in migration and adhesion can be explained by the pro-apoptotic effects of increasing doses of vitamin D3 (Fig. 3). As shown in Fig. 3, panel a, exposure of the A2780 ovarian cancer cell line to vitamin D3 resulted in an increase in the number of early and late apoptotic cells, which correlated with impaired vitamin D3 signaling in these cells (Fig. 3, panel b).Fig. 3

Bottom Line: We evaluated expression of Vitamin D3 receptor (VDR) in these cells as well as effect of vitamin D3 exposure on cell proliferation and migration.We also found that the ESD3 murine immortalized embryonic stem cell line and normal, pluripotent, germline-marker-positive very small embryonic-like stem cells (VSELs) isolated from adult tissues are stimulated by vitamin D3, which suggests that vitamin D3 affects the earliest stages of embryogenesis.We found that however all normal and malignant germ-line derived cells express functional VDR, Vitamin D3 differently affects their proliferation and migration.

View Article: PubMed Central - PubMed

Affiliation: Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, 500 S. Floyd Street, Rm. 107, Louisville, KY, 40202, USA.

ABSTRACT

Background: Deficiency in Vitamin D3 (cholecalciferol) may predispose to some malignancies, including gonadal tumors and in experimental models vitamin D3 has been proven to inhibit the growth of cancer cells. To learn more about the potential role of vitamin D3 in cancerogenesis, we evaluated the expression and functionality of the vitamin D receptor (VDR) and its role in metastasis of ovarian cancer cells and of murine and human teratocarcinoma cell lines.

Methods: In our studies we employed murine embrynic stem cells (ESD3), murine (P19) and human (NTERA-2) teratocarcimona cells lines, human ovarian cancer cells (A2780) as well as purified murine and human purified very small embryonic like stem cells (VSELs). We evaluated expression of Vitamin D3 receptor (VDR) in these cells as well as effect of vitamin D3 exposure on cell proliferation and migration.

Results: We here provide also more evidence for the role of vitamin D3 in germline-derived malignancies, and this evidence supports the proposal that vitamin D3 treatment inhibits growth and metastatic potential of several germline-derived malignancies. We also found that the ESD3 murine immortalized embryonic stem cell line and normal, pluripotent, germline-marker-positive very small embryonic-like stem cells (VSELs) isolated from adult tissues are stimulated by vitamin D3, which suggests that vitamin D3 affects the earliest stages of embryogenesis.

Conclusions: We found that however all normal and malignant germ-line derived cells express functional VDR, Vitamin D3 differently affects their proliferation and migration. We postulate that while Vitamin D3 as anticancer drug inhibits proliferation of malignant cells, it may protect normal stem cells that play an important role in development and tissue/organ regeneration.

No MeSH data available.


Related in: MedlinePlus