Cargando…
Vitamin D and its low calcemic analogs modulate the anticancer properties of cisplatin and dacarbazine in the human melanoma A375 cell line
Melanoma represents a significant challenge in cancer treatment due to the high drug resistance of melanomas and the patient mortality rate. This study presents data indicating that nanomolar concentrations of the hormonally active form of vitamin D, 1α,25-dihydroxyvitamin D3 [1α,25(OH)(2)D3], its n...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6411347/ https://www.ncbi.nlm.nih.gov/pubmed/30968156 http://dx.doi.org/10.3892/ijo.2019.4725 |
_version_ | 1783402377743695872 |
---|---|
author | Piotrowska, Anna Wierzbicka, Justyna Rybarczyk, Agnieszka Tuckey, Robert C. Slominski, Andrzej T. Żmijewski, Michał A. |
author_facet | Piotrowska, Anna Wierzbicka, Justyna Rybarczyk, Agnieszka Tuckey, Robert C. Slominski, Andrzej T. Żmijewski, Michał A. |
author_sort | Piotrowska, Anna |
collection | PubMed |
description | Melanoma represents a significant challenge in cancer treatment due to the high drug resistance of melanomas and the patient mortality rate. This study presents data indicating that nanomolar concentrations of the hormonally active form of vitamin D, 1α,25-dihydroxyvitamin D3 [1α,25(OH)(2)D3], its non-calcemic analogues 20S-hydroxyvitamin D3 and 21-hydroxypregnacalciferol, as well as the low-calcemic synthetic analog calcipotriol, modulate the efficacy of the anticancer drugs cisplatin and dacarbazine. It was observed that vitamin D analogs sensitized melanoma A375 cells to hydrogen peroxide used as an inducer of oxidative stress. On the other hand, only 1α,25(OH)(2)D3 resulted in a minor, but significant effect on the proliferation of melanoma cells treated simultaneously with dacarbazine, but not cisplatin. Notably, cisplatin (300 µM) exhibited a higher overall antiproliferative activity than dacarbazine. Cisplatin treatment of melanoma cells resulted in an induction of apoptosis as demonstrated by flow cytometry (accumulation of cells at the subG(1) phase of the cell cycle), whereas dacarbazine caused G(1)/G(0) cell cycle arrest, with the effects being improved by pre-treatment with vitamin D analogs. Treatment with cisplatin resulted in an initial increase in the level of reactive oxygen species (ROS). Dacarbazine caused transient stimulation of ROS levels and the mitochondrial membrane potential (Δψ(m)) (after 1 or 3 h of treatment, respectively), but the effect was not detectable following prolonged (24 h) incubation with the drug. Vitamin D exhibited modulatory effects on the cells treated with dacarbazine, decreasing the half maximal inhibitory concentration (IC(50)) for the drug, stimulating G(1)/G(0) arrest and causing a marked decrease in Δψ(m). Finally, cisplatin, dacarbazine and 1α,25(OH)(2)D3 displayed modulatory effects on the expression of ROS and vitamin D-associated genes in the melanoma A375 cells. In conclusion, nanomolar concentrations of 1,25(OH)(2)D(3) only had minor effects on the proliferation of melanoma cells treated with dacarbazine, decreasing the relative IC(50) value. However, co-treatment with vitamin D analogs resulted in the modulation of cell cycle and ROS responses, and affected gene expression, suggesting possible crosstalk between the signaling pathways of vitamin D and the anticancer drugs used in this study. |
format | Online Article Text |
id | pubmed-6411347 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-64113472019-03-19 Vitamin D and its low calcemic analogs modulate the anticancer properties of cisplatin and dacarbazine in the human melanoma A375 cell line Piotrowska, Anna Wierzbicka, Justyna Rybarczyk, Agnieszka Tuckey, Robert C. Slominski, Andrzej T. Żmijewski, Michał A. Int J Oncol Articles Melanoma represents a significant challenge in cancer treatment due to the high drug resistance of melanomas and the patient mortality rate. This study presents data indicating that nanomolar concentrations of the hormonally active form of vitamin D, 1α,25-dihydroxyvitamin D3 [1α,25(OH)(2)D3], its non-calcemic analogues 20S-hydroxyvitamin D3 and 21-hydroxypregnacalciferol, as well as the low-calcemic synthetic analog calcipotriol, modulate the efficacy of the anticancer drugs cisplatin and dacarbazine. It was observed that vitamin D analogs sensitized melanoma A375 cells to hydrogen peroxide used as an inducer of oxidative stress. On the other hand, only 1α,25(OH)(2)D3 resulted in a minor, but significant effect on the proliferation of melanoma cells treated simultaneously with dacarbazine, but not cisplatin. Notably, cisplatin (300 µM) exhibited a higher overall antiproliferative activity than dacarbazine. Cisplatin treatment of melanoma cells resulted in an induction of apoptosis as demonstrated by flow cytometry (accumulation of cells at the subG(1) phase of the cell cycle), whereas dacarbazine caused G(1)/G(0) cell cycle arrest, with the effects being improved by pre-treatment with vitamin D analogs. Treatment with cisplatin resulted in an initial increase in the level of reactive oxygen species (ROS). Dacarbazine caused transient stimulation of ROS levels and the mitochondrial membrane potential (Δψ(m)) (after 1 or 3 h of treatment, respectively), but the effect was not detectable following prolonged (24 h) incubation with the drug. Vitamin D exhibited modulatory effects on the cells treated with dacarbazine, decreasing the half maximal inhibitory concentration (IC(50)) for the drug, stimulating G(1)/G(0) arrest and causing a marked decrease in Δψ(m). Finally, cisplatin, dacarbazine and 1α,25(OH)(2)D3 displayed modulatory effects on the expression of ROS and vitamin D-associated genes in the melanoma A375 cells. In conclusion, nanomolar concentrations of 1,25(OH)(2)D(3) only had minor effects on the proliferation of melanoma cells treated with dacarbazine, decreasing the relative IC(50) value. However, co-treatment with vitamin D analogs resulted in the modulation of cell cycle and ROS responses, and affected gene expression, suggesting possible crosstalk between the signaling pathways of vitamin D and the anticancer drugs used in this study. D.A. Spandidos 2019-02-25 /pmc/articles/PMC6411347/ /pubmed/30968156 http://dx.doi.org/10.3892/ijo.2019.4725 Text en Copyright © 2019, Spandidos Publications |
spellingShingle | Articles Piotrowska, Anna Wierzbicka, Justyna Rybarczyk, Agnieszka Tuckey, Robert C. Slominski, Andrzej T. Żmijewski, Michał A. Vitamin D and its low calcemic analogs modulate the anticancer properties of cisplatin and dacarbazine in the human melanoma A375 cell line |
title | Vitamin D and its low calcemic analogs modulate the anticancer properties of cisplatin and dacarbazine in the human melanoma A375 cell line |
title_full | Vitamin D and its low calcemic analogs modulate the anticancer properties of cisplatin and dacarbazine in the human melanoma A375 cell line |
title_fullStr | Vitamin D and its low calcemic analogs modulate the anticancer properties of cisplatin and dacarbazine in the human melanoma A375 cell line |
title_full_unstemmed | Vitamin D and its low calcemic analogs modulate the anticancer properties of cisplatin and dacarbazine in the human melanoma A375 cell line |
title_short | Vitamin D and its low calcemic analogs modulate the anticancer properties of cisplatin and dacarbazine in the human melanoma A375 cell line |
title_sort | vitamin d and its low calcemic analogs modulate the anticancer properties of cisplatin and dacarbazine in the human melanoma a375 cell line |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6411347/ https://www.ncbi.nlm.nih.gov/pubmed/30968156 http://dx.doi.org/10.3892/ijo.2019.4725 |
work_keys_str_mv | AT piotrowskaanna vitamindanditslowcalcemicanalogsmodulatetheanticancerpropertiesofcisplatinanddacarbazineinthehumanmelanomaa375cellline AT wierzbickajustyna vitamindanditslowcalcemicanalogsmodulatetheanticancerpropertiesofcisplatinanddacarbazineinthehumanmelanomaa375cellline AT rybarczykagnieszka vitamindanditslowcalcemicanalogsmodulatetheanticancerpropertiesofcisplatinanddacarbazineinthehumanmelanomaa375cellline AT tuckeyrobertc vitamindanditslowcalcemicanalogsmodulatetheanticancerpropertiesofcisplatinanddacarbazineinthehumanmelanomaa375cellline AT slominskiandrzejt vitamindanditslowcalcemicanalogsmodulatetheanticancerpropertiesofcisplatinanddacarbazineinthehumanmelanomaa375cellline AT zmijewskimichała vitamindanditslowcalcemicanalogsmodulatetheanticancerpropertiesofcisplatinanddacarbazineinthehumanmelanomaa375cellline |