Vitamin D Analogs Regulate the Vitamin D System and Cell Viability in Ovarian Cancer Cells

• Published in: International journal of molecular sciences 2021-12, Vol.23 (1), p.172
• Main Authors: Piatek, Karina, Kutner, Andrzej, Cacsire Castillo-Tong, Dan, Manhardt, Teresa, Kupper, Nadja, Nowak, Urszula, Chodyński, Michał, Marcinkowska, Ewa, Kallay, Enikö, Schepelmann, Martin
• Format: Article
• Language: English
• Subjects: Analogs; Antineoplastic Agents - metabolism; Antineoplastic Agents - pharmacology; Antitumor activity; Calciferol; Calcitriol; Cancer therapies; Cell Line, Tumor; Cell number; Cell Survival; Cell viability; Cells, Cultured; Cytochrome; Ergocalciferols - metabolism; Ergocalciferols - pharmacology; Female; Gene expression; Gene Expression Regulation, Neoplastic; Humans; Hydroxylase; Hypercalcemia; Leukemia; Ligands; Ovarian cancer; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - enzymology; Ovarian Neoplasms - metabolism; Proteins; Receptors, Calcitriol - genetics; Transcription factors; Tumor cell lines; Tumors; Vitamin D; Vitamin D - analogs & derivatives; Vitamin D - pharmacology; Vitamin D receptors; Vitamin D-24-hydroxylase; Vitamin D3; Vitamin D3 24-Hydroxylase - genetics
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23010172

Ovarian cancer (OC) is one of the most lethal cancers in women. The active form of vitamin D , 1,25-dihydroxyvitamin D (1,25D , 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. 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 D 24-hydroxylase , 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 , and the vitamin D receptor (VDR). 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: EC = 2.98 ± 1.10 nmol/L, in 14433 cells: EC = 0.92 ± 0.20 nmol/L), while PRI-1907 was the least active one (in 13781 cells: EC = n/d, in 14433 cells: EC = 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. The an1,25Ds had different potencies in the HGSOC cell lines and their efficacy in increasing 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.