Differential antitumor effects of vitamin D analogues on colorectal carcinoma in culture

J.M. Wierzbicka, A. Binek, T. Ahrends, J.D. Nowac Ka, A. Szydłowska, T. Wąsiewic Z, P.M. Wierzbicki, R. Sądej, Robert Tuckey, A.T. Slominski, J. Chybicki, K. Adrych, Z. Kmieć, M.A. Zmijewski

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Colorectal cancer (CRC) is an emerging global problem with the rapid increase in its incidence being associated with an unhealthy lifestyle. Epidemiological studies have shown that decreased levels of vitamin D3 significantly increases the risk of CRC. Furthermore, negative effects of vitamin D3 deficiency can be compensated by appropriate supplementation. Vitamin D3 was shown to inhibit growth and induce differentiation of cancer cells, however, excessive vitamin D3 intake leads to hypercalcemia. Thus, development of efficient vitamin D3 analogues with limited impact on calcium homeostasis is an important scientific and clinically relevant task. The aims of the present study were to compare the antiproliferative potential of classic vitamin D3 metabolites (1α,25(OH)2D3 and 25(OH)D3) with selected low calcemic analogues (calcipotriol and 20(OH)D3) on CRC cell lines and to investigate the expression of vitamin D-related genes in CRC cell lines and clinical samples. Vitamin D3 analogues exerted anti-proliferative effects on all CRC cell lines tested. Calcipotriol proved to be as potent as 1α,25(OH)2D3 and had more efficacy than 20-hydroxyvitamin D3. In addition, the analogs tested effectively inhibited the formation of colonies in Matrigel. The expression of genes involved in 1α,25(OH)2D3 signaling and metabolism varied in cell lines analysed, which explains in part their different sensitivities to the various analogues. In CRC biopsies, there was decreased VDR expression in tumor samples in comparison to the surgical margin and healthy colon samples (p
Original languageEnglish
Pages (from-to)1084-1096
JournalInternational Journal of Oncology
Volume47
Issue number3
DOIs
Publication statusPublished - 2015

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Cholecalciferol
Vitamin D
Colorectal Neoplasms
Cell Line
Avitaminosis
Hypercalcemia
Life Style
Epidemiologic Studies
Cell Differentiation
Neoplasms
Colon
Homeostasis
Calcium
Biopsy
Gene Expression
Incidence
Growth
Genes

Cite this

Wierzbicka, J. M., Binek, A., Ahrends, T., Nowac Ka, J. D., Szydłowska, A., Wąsiewic Z, T., ... Zmijewski, M. A. (2015). Differential antitumor effects of vitamin D analogues on colorectal carcinoma in culture. International Journal of Oncology, 47(3), 1084-1096. https://doi.org/10.3892/ijo.2015.3088
Wierzbicka, J.M. ; Binek, A. ; Ahrends, T. ; Nowac Ka, J.D. ; Szydłowska, A. ; Wąsiewic Z, T. ; Wierzbicki, P.M. ; Sądej, R. ; Tuckey, Robert ; Slominski, A.T. ; Chybicki, J. ; Adrych, K. ; Kmieć, Z. ; Zmijewski, M.A. / Differential antitumor effects of vitamin D analogues on colorectal carcinoma in culture. In: International Journal of Oncology. 2015 ; Vol. 47, No. 3. pp. 1084-1096.
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abstract = "Colorectal cancer (CRC) is an emerging global problem with the rapid increase in its incidence being associated with an unhealthy lifestyle. Epidemiological studies have shown that decreased levels of vitamin D3 significantly increases the risk of CRC. Furthermore, negative effects of vitamin D3 deficiency can be compensated by appropriate supplementation. Vitamin D3 was shown to inhibit growth and induce differentiation of cancer cells, however, excessive vitamin D3 intake leads to hypercalcemia. Thus, development of efficient vitamin D3 analogues with limited impact on calcium homeostasis is an important scientific and clinically relevant task. The aims of the present study were to compare the antiproliferative potential of classic vitamin D3 metabolites (1α,25(OH)2D3 and 25(OH)D3) with selected low calcemic analogues (calcipotriol and 20(OH)D3) on CRC cell lines and to investigate the expression of vitamin D-related genes in CRC cell lines and clinical samples. Vitamin D3 analogues exerted anti-proliferative effects on all CRC cell lines tested. Calcipotriol proved to be as potent as 1α,25(OH)2D3 and had more efficacy than 20-hydroxyvitamin D3. In addition, the analogs tested effectively inhibited the formation of colonies in Matrigel. The expression of genes involved in 1α,25(OH)2D3 signaling and metabolism varied in cell lines analysed, which explains in part their different sensitivities to the various analogues. In CRC biopsies, there was decreased VDR expression in tumor samples in comparison to the surgical margin and healthy colon samples (p",
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Wierzbicka, JM, Binek, A, Ahrends, T, Nowac Ka, JD, Szydłowska, A, Wąsiewic Z, T, Wierzbicki, PM, Sądej, R, Tuckey, R, Slominski, AT, Chybicki, J, Adrych, K, Kmieć, Z & Zmijewski, MA 2015, 'Differential antitumor effects of vitamin D analogues on colorectal carcinoma in culture' International Journal of Oncology, vol. 47, no. 3, pp. 1084-1096. https://doi.org/10.3892/ijo.2015.3088

Differential antitumor effects of vitamin D analogues on colorectal carcinoma in culture. / Wierzbicka, J.M.; Binek, A.; Ahrends, T.; Nowac Ka, J.D.; Szydłowska, A.; Wąsiewic Z, T.; Wierzbicki, P.M.; Sądej, R.; Tuckey, Robert; Slominski, A.T.; Chybicki, J.; Adrych, K.; Kmieć, Z.; Zmijewski, M.A.

In: International Journal of Oncology, Vol. 47, No. 3, 2015, p. 1084-1096.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Differential antitumor effects of vitamin D analogues on colorectal carcinoma in culture

AU - Wierzbicka, J.M.

AU - Binek, A.

AU - Ahrends, T.

AU - Nowac Ka, J.D.

AU - Szydłowska, A.

AU - Wąsiewic Z, T.

AU - Wierzbicki, P.M.

AU - Sądej, R.

AU - Tuckey, Robert

AU - Slominski, A.T.

AU - Chybicki, J.

AU - Adrych, K.

AU - Kmieć, Z.

AU - Zmijewski, M.A.

PY - 2015

Y1 - 2015

N2 - Colorectal cancer (CRC) is an emerging global problem with the rapid increase in its incidence being associated with an unhealthy lifestyle. Epidemiological studies have shown that decreased levels of vitamin D3 significantly increases the risk of CRC. Furthermore, negative effects of vitamin D3 deficiency can be compensated by appropriate supplementation. Vitamin D3 was shown to inhibit growth and induce differentiation of cancer cells, however, excessive vitamin D3 intake leads to hypercalcemia. Thus, development of efficient vitamin D3 analogues with limited impact on calcium homeostasis is an important scientific and clinically relevant task. The aims of the present study were to compare the antiproliferative potential of classic vitamin D3 metabolites (1α,25(OH)2D3 and 25(OH)D3) with selected low calcemic analogues (calcipotriol and 20(OH)D3) on CRC cell lines and to investigate the expression of vitamin D-related genes in CRC cell lines and clinical samples. Vitamin D3 analogues exerted anti-proliferative effects on all CRC cell lines tested. Calcipotriol proved to be as potent as 1α,25(OH)2D3 and had more efficacy than 20-hydroxyvitamin D3. In addition, the analogs tested effectively inhibited the formation of colonies in Matrigel. The expression of genes involved in 1α,25(OH)2D3 signaling and metabolism varied in cell lines analysed, which explains in part their different sensitivities to the various analogues. In CRC biopsies, there was decreased VDR expression in tumor samples in comparison to the surgical margin and healthy colon samples (p

AB - Colorectal cancer (CRC) is an emerging global problem with the rapid increase in its incidence being associated with an unhealthy lifestyle. Epidemiological studies have shown that decreased levels of vitamin D3 significantly increases the risk of CRC. Furthermore, negative effects of vitamin D3 deficiency can be compensated by appropriate supplementation. Vitamin D3 was shown to inhibit growth and induce differentiation of cancer cells, however, excessive vitamin D3 intake leads to hypercalcemia. Thus, development of efficient vitamin D3 analogues with limited impact on calcium homeostasis is an important scientific and clinically relevant task. The aims of the present study were to compare the antiproliferative potential of classic vitamin D3 metabolites (1α,25(OH)2D3 and 25(OH)D3) with selected low calcemic analogues (calcipotriol and 20(OH)D3) on CRC cell lines and to investigate the expression of vitamin D-related genes in CRC cell lines and clinical samples. Vitamin D3 analogues exerted anti-proliferative effects on all CRC cell lines tested. Calcipotriol proved to be as potent as 1α,25(OH)2D3 and had more efficacy than 20-hydroxyvitamin D3. In addition, the analogs tested effectively inhibited the formation of colonies in Matrigel. The expression of genes involved in 1α,25(OH)2D3 signaling and metabolism varied in cell lines analysed, which explains in part their different sensitivities to the various analogues. In CRC biopsies, there was decreased VDR expression in tumor samples in comparison to the surgical margin and healthy colon samples (p

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DO - 10.3892/ijo.2015.3088

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VL - 47

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JO - International Journal of Oncology

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Wierzbicka JM, Binek A, Ahrends T, Nowac Ka JD, Szydłowska A, Wąsiewic Z T et al. Differential antitumor effects of vitamin D analogues on colorectal carcinoma in culture. International Journal of Oncology. 2015;47(3):1084-1096. https://doi.org/10.3892/ijo.2015.3088