Vitamin D derivatives enhance cytotoxic effects of H2O2 or cisplatin on human keratinocytes

A. Piotrowska, J. Wierzbicka, T. Ślebioda, M. Woźniak, Robert Tuckey, A.T. Slominski, M.A. Zmijewski

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

© 2016 Elsevier Inc. Although the skin production of vitamin D is initiated by ultraviolet radiation type B (UVB), the role vitamin D plays in antioxidative or pro-oxidative responses remains to be elucidated. We have used immortalized human HaCaT keratinocytes as a model of proliferating epidermal cells to test the influence of vitamin D on cellular response to H2O2 or the anti-cancer drug, cisplatin. Incubation of keratinocytes with 1,25(OH)2D3 or its low calcemic analogues, 20(OH)D3, 21(OH)pD or calcipotriol, sensitized cells to ROS resulting in more potent inhibition of keratinocyte proliferation by H2O2 in the presence of vitamin D compounds. These results were supported by cell cycle and apoptosis analyses, and measurement of the mitochondrial transmembrane potentials (MMP), however some unique properties of individual secosteroids were observed. Furthermore, in HaCaT keratinocytes treated with H2O2, 1,25(OH)2D3, 21(OH)pD and calcipotriol stimulated the expression of SOD1 and CAT genes, but not SOD2, indicating a possible role of mitochondria in ROS-modulated cell death. 1,25(OH)2D3 also showed a short-term, protective effect on HaCaT keratinocytes, as exemplified by the inhibition of apoptosis and the maintenance of MMP. However, with prolonged incubation with H2O2 or cisplatin, 1,25(OH)2D3 caused an acceleration in the death of the keratinocytes. Therefore, we propose that lead vitamin D derivatives can protect the epidermis against neoplastic transformation secondary to oxidative or UV-induced stress through activation of vitamin D-signaling. Furthermore, our data suggest that treatment with low calcemic vitamin D analogues or the maintenance of optimal level of vitamin D by proper supplementation, can enhance the anticancer efficacy of cisplatin
Original languageEnglish
Pages (from-to)49-61
JournalSteroids
Volume110
DOIs
Publication statusPublished - 2016

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Keratinocytes
Vitamin D
Cisplatin
Derivatives
Membrane Potentials
Secosteroids
Maintenance
Apoptosis
Mitochondria
Cell death
Epidermis
Ultraviolet radiation
Skin
Cell Cycle
Cell Death
Genes
Chemical activation
Cells
Radiation
Pharmaceutical Preparations

Cite this

Piotrowska, A., Wierzbicka, J., Ślebioda, T., Woźniak, M., Tuckey, R., Slominski, A. T., & Zmijewski, M. A. (2016). Vitamin D derivatives enhance cytotoxic effects of H2O2 or cisplatin on human keratinocytes. Steroids, 110, 49-61. https://doi.org/10.1016/j.steroids.2016.04.002
Piotrowska, A. ; Wierzbicka, J. ; Ślebioda, T. ; Woźniak, M. ; Tuckey, Robert ; Slominski, A.T. ; Zmijewski, M.A. / Vitamin D derivatives enhance cytotoxic effects of H2O2 or cisplatin on human keratinocytes. In: Steroids. 2016 ; Vol. 110. pp. 49-61.
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abstract = "{\circledC} 2016 Elsevier Inc. Although the skin production of vitamin D is initiated by ultraviolet radiation type B (UVB), the role vitamin D plays in antioxidative or pro-oxidative responses remains to be elucidated. We have used immortalized human HaCaT keratinocytes as a model of proliferating epidermal cells to test the influence of vitamin D on cellular response to H2O2 or the anti-cancer drug, cisplatin. Incubation of keratinocytes with 1,25(OH)2D3 or its low calcemic analogues, 20(OH)D3, 21(OH)pD or calcipotriol, sensitized cells to ROS resulting in more potent inhibition of keratinocyte proliferation by H2O2 in the presence of vitamin D compounds. These results were supported by cell cycle and apoptosis analyses, and measurement of the mitochondrial transmembrane potentials (MMP), however some unique properties of individual secosteroids were observed. Furthermore, in HaCaT keratinocytes treated with H2O2, 1,25(OH)2D3, 21(OH)pD and calcipotriol stimulated the expression of SOD1 and CAT genes, but not SOD2, indicating a possible role of mitochondria in ROS-modulated cell death. 1,25(OH)2D3 also showed a short-term, protective effect on HaCaT keratinocytes, as exemplified by the inhibition of apoptosis and the maintenance of MMP. However, with prolonged incubation with H2O2 or cisplatin, 1,25(OH)2D3 caused an acceleration in the death of the keratinocytes. Therefore, we propose that lead vitamin D derivatives can protect the epidermis against neoplastic transformation secondary to oxidative or UV-induced stress through activation of vitamin D-signaling. Furthermore, our data suggest that treatment with low calcemic vitamin D analogues or the maintenance of optimal level of vitamin D by proper supplementation, can enhance the anticancer efficacy of cisplatin",
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Piotrowska, A, Wierzbicka, J, Ślebioda, T, Woźniak, M, Tuckey, R, Slominski, AT & Zmijewski, MA 2016, 'Vitamin D derivatives enhance cytotoxic effects of H2O2 or cisplatin on human keratinocytes' Steroids, vol. 110, pp. 49-61. https://doi.org/10.1016/j.steroids.2016.04.002

Vitamin D derivatives enhance cytotoxic effects of H2O2 or cisplatin on human keratinocytes. / Piotrowska, A.; Wierzbicka, J.; Ślebioda, T.; Woźniak, M.; Tuckey, Robert; Slominski, A.T.; Zmijewski, M.A.

In: Steroids, Vol. 110, 2016, p. 49-61.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Vitamin D derivatives enhance cytotoxic effects of H2O2 or cisplatin on human keratinocytes

AU - Piotrowska, A.

AU - Wierzbicka, J.

AU - Ślebioda, T.

AU - Woźniak, M.

AU - Tuckey, Robert

AU - Slominski, A.T.

AU - Zmijewski, M.A.

PY - 2016

Y1 - 2016

N2 - © 2016 Elsevier Inc. Although the skin production of vitamin D is initiated by ultraviolet radiation type B (UVB), the role vitamin D plays in antioxidative or pro-oxidative responses remains to be elucidated. We have used immortalized human HaCaT keratinocytes as a model of proliferating epidermal cells to test the influence of vitamin D on cellular response to H2O2 or the anti-cancer drug, cisplatin. Incubation of keratinocytes with 1,25(OH)2D3 or its low calcemic analogues, 20(OH)D3, 21(OH)pD or calcipotriol, sensitized cells to ROS resulting in more potent inhibition of keratinocyte proliferation by H2O2 in the presence of vitamin D compounds. These results were supported by cell cycle and apoptosis analyses, and measurement of the mitochondrial transmembrane potentials (MMP), however some unique properties of individual secosteroids were observed. Furthermore, in HaCaT keratinocytes treated with H2O2, 1,25(OH)2D3, 21(OH)pD and calcipotriol stimulated the expression of SOD1 and CAT genes, but not SOD2, indicating a possible role of mitochondria in ROS-modulated cell death. 1,25(OH)2D3 also showed a short-term, protective effect on HaCaT keratinocytes, as exemplified by the inhibition of apoptosis and the maintenance of MMP. However, with prolonged incubation with H2O2 or cisplatin, 1,25(OH)2D3 caused an acceleration in the death of the keratinocytes. Therefore, we propose that lead vitamin D derivatives can protect the epidermis against neoplastic transformation secondary to oxidative or UV-induced stress through activation of vitamin D-signaling. Furthermore, our data suggest that treatment with low calcemic vitamin D analogues or the maintenance of optimal level of vitamin D by proper supplementation, can enhance the anticancer efficacy of cisplatin

AB - © 2016 Elsevier Inc. Although the skin production of vitamin D is initiated by ultraviolet radiation type B (UVB), the role vitamin D plays in antioxidative or pro-oxidative responses remains to be elucidated. We have used immortalized human HaCaT keratinocytes as a model of proliferating epidermal cells to test the influence of vitamin D on cellular response to H2O2 or the anti-cancer drug, cisplatin. Incubation of keratinocytes with 1,25(OH)2D3 or its low calcemic analogues, 20(OH)D3, 21(OH)pD or calcipotriol, sensitized cells to ROS resulting in more potent inhibition of keratinocyte proliferation by H2O2 in the presence of vitamin D compounds. These results were supported by cell cycle and apoptosis analyses, and measurement of the mitochondrial transmembrane potentials (MMP), however some unique properties of individual secosteroids were observed. Furthermore, in HaCaT keratinocytes treated with H2O2, 1,25(OH)2D3, 21(OH)pD and calcipotriol stimulated the expression of SOD1 and CAT genes, but not SOD2, indicating a possible role of mitochondria in ROS-modulated cell death. 1,25(OH)2D3 also showed a short-term, protective effect on HaCaT keratinocytes, as exemplified by the inhibition of apoptosis and the maintenance of MMP. However, with prolonged incubation with H2O2 or cisplatin, 1,25(OH)2D3 caused an acceleration in the death of the keratinocytes. Therefore, we propose that lead vitamin D derivatives can protect the epidermis against neoplastic transformation secondary to oxidative or UV-induced stress through activation of vitamin D-signaling. Furthermore, our data suggest that treatment with low calcemic vitamin D analogues or the maintenance of optimal level of vitamin D by proper supplementation, can enhance the anticancer efficacy of cisplatin

U2 - 10.1016/j.steroids.2016.04.002

DO - 10.1016/j.steroids.2016.04.002

M3 - Article

VL - 110

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JO - Steroids

JF - Steroids

SN - 0039-128X

ER -