Vitamin D Analogs Regulate the Vitamin D System and Cell Viability in Ovarian Cancer Cells
| Autor: | Karina Piatek, Andrzej Kutner, Dan Cacsire Castillo-Tong, Teresa Manhardt, Nadja Kupper, Urszula Nowak, Michał Chodyński, Ewa Marcinkowska, Enikö Kallay, Martin Schepelmann |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
high-grade serous ovarian cancer cells
Cell Survival QH301-705.5 proliferation Antineoplastic Agents vitamin D Catalysis Article Inorganic Chemistry Cell Line Tumor Humans Physical and Theoretical Chemistry Biology (General) Vitamin D3 24-Hydroxylase Molecular Biology QD1-999 Spectroscopy Cells Cultured Ovarian Neoplasms Organic Chemistry General Medicine Computer Science Applications vitamin D analogs 25 vitamin D 24-hydroxylase CYP24A1 Gene Expression Regulation Neoplastic Chemistry Ergocalciferols Receptors Calcitriol Female |
| Zdroj: | International Journal of Molecular Sciences, Vol 23, Iss 172, p 172 (2022) International Journal of Molecular Sciences International Journal of Molecular Sciences; Volume 23; Issue 1; Pages: 172 |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | Background: Ovarian cancer (OC) is one of the most lethal cancers in women. The active form of vitamin D3, 1,25-dihydroxyvitamin D3 (1,25D3, calcitriol) has anticancer activity in several cancers, including ovarian cancer, but the required pharmacological doses may cause hypercalcemia. We hypothesized that newly developed, low calcemic, vitamin D analogs (an1,25Ds) may be used as anticancer agents instead of calcitriol in ovarian cancer cells. Methods: We used two patient-derived high-grade serous ovarian cancer (HGSOC) cell lines with low (13781) and high (14433) mRNA expression levels of the gene encoding 1,25-dihydroxyvitamin D3 24-hydroxylase CYP24A1, one of the main target genes of calcitriol. We tested the effect of calcitriol and four structurally related series of an1,25Ds (PRI-1906, PRI-1907, PRI-5201, PRI-5202) on cell number, viability, the expression of CYP24A1, and the vitamin D receptor (VDR). Results: CYP24A1 mRNA expression increased in a concentration-dependent manner after treatment with all compounds. In both cell lines, after 4 h, PRI-5202 was the most potent analog (in 13781 cells: EC50 = 2.98 ± 1.10 nmol/L, in 14433 cells: EC50 = 0.92 ± 0.20 nmol/L), while PRI-1907 was the least active one (in 13781 cells: EC50 = n/d, in 14433 cells: EC50 = n/d). This difference among the analogs disappeared after 5 days of treatment. The 13781 cells were more sensitive to the an1,25Ds compared with 14433 cells. The an1,25Ds increased nuclear VDR levels and reduced cell viability, but only in the 13781 cell line. Conclusions: The an1,25Ds had different potencies in the HGSOC cell lines and their efficacy in increasing CYP24A1 expression was cell line- and chemical structure-dependent. Therefore, choosing sensitive cancer cell lines and further optimization of the analogs’ structure might lead to new treatment options against ovarian cancer. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|