25-Hydroxycholecalciferol Inhibits Cell Growth and Induces Apoptosis in SiHa Cervical Cells via Autocrine Vitamin D Metabolism
Preclinical studies show that the anticancer actions of vitamin D metabolites are mediated by apoptosis, inhibition of cell proliferation and induction of cell cycle arrest. Cervical cancer cells express an autocrine vitamin D metabolising system (VDMS) comprised of a vitamin D receptor, vitamin D c...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/3/871 |
| _version_ | 1797613327878193152 |
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| author | Rivak Punchoo Greta Dreyer Tahir S. Pillay |
| author_facet | Rivak Punchoo Greta Dreyer Tahir S. Pillay |
| author_sort | Rivak Punchoo |
| collection | DOAJ |
| description | Preclinical studies show that the anticancer actions of vitamin D metabolites are mediated by apoptosis, inhibition of cell proliferation and induction of cell cycle arrest. Cervical cancer cells express an autocrine vitamin D metabolising system (VDMS) comprised of a vitamin D receptor, vitamin D catabolic enzyme (CYP24A1), and the activating enzyme of 25-hydroxycholecalciferol (25(OH)D3), CYP27B1. We assessed the anticancer effects of 25(OH)D3 at clinically relevant concentrations on a cervical squamous cell cancer cell line, SiHa. We evaluated cell health parameters (cell count, viability, and cell cycle), cell death modes (apoptosis, autophagic-dependent death, and necrosis by flow cytometry and transmission electron microscopy), and autocrine VDMS gene and protein expression by qPCR and Western blot, respectively. Our study demonstrates that physiological and supraphysiological doses of 25(OH)D3 inhibit cell growth and viability and induce biochemical and morphological apoptosis in SiHa cells. These growth effects are mediated by alteration in the VDMS gene and protein expression, with prominent negative feedback at supraphysiological treatment dose. These data identify promising therapeutic potential of 25(OH)D3 in cervical cancer, which warrants further clinical translational investigations. |
| first_indexed | 2024-03-11T06:53:21Z |
| format | Article |
| id | doaj.art-3b58bf73b6a948439b4f77a02af36f1b |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-11T06:53:21Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-3b58bf73b6a948439b4f77a02af36f1b2023-11-17T09:46:51ZengMDPI AGBiomedicines2227-90592023-03-0111387110.3390/biomedicines1103087125-Hydroxycholecalciferol Inhibits Cell Growth and Induces Apoptosis in SiHa Cervical Cells via Autocrine Vitamin D MetabolismRivak Punchoo0Greta Dreyer1Tahir S. Pillay2Tshwane Academic Division, National Health Laboratory Service (NHLS), Pretoria 0001, South AfricaDepartment of Obstetrics and Gynaecology, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South AfricaTshwane Academic Division, National Health Laboratory Service (NHLS), Pretoria 0001, South AfricaPreclinical studies show that the anticancer actions of vitamin D metabolites are mediated by apoptosis, inhibition of cell proliferation and induction of cell cycle arrest. Cervical cancer cells express an autocrine vitamin D metabolising system (VDMS) comprised of a vitamin D receptor, vitamin D catabolic enzyme (CYP24A1), and the activating enzyme of 25-hydroxycholecalciferol (25(OH)D3), CYP27B1. We assessed the anticancer effects of 25(OH)D3 at clinically relevant concentrations on a cervical squamous cell cancer cell line, SiHa. We evaluated cell health parameters (cell count, viability, and cell cycle), cell death modes (apoptosis, autophagic-dependent death, and necrosis by flow cytometry and transmission electron microscopy), and autocrine VDMS gene and protein expression by qPCR and Western blot, respectively. Our study demonstrates that physiological and supraphysiological doses of 25(OH)D3 inhibit cell growth and viability and induce biochemical and morphological apoptosis in SiHa cells. These growth effects are mediated by alteration in the VDMS gene and protein expression, with prominent negative feedback at supraphysiological treatment dose. These data identify promising therapeutic potential of 25(OH)D3 in cervical cancer, which warrants further clinical translational investigations.https://www.mdpi.com/2227-9059/11/3/871cervical cancerSiHa25-hydroxycholecalciferolapoptosisvitamin D metabolising system24-hydroxylase (CYP24A1) |
| spellingShingle | Rivak Punchoo Greta Dreyer Tahir S. Pillay 25-Hydroxycholecalciferol Inhibits Cell Growth and Induces Apoptosis in SiHa Cervical Cells via Autocrine Vitamin D Metabolism Biomedicines cervical cancer SiHa 25-hydroxycholecalciferol apoptosis vitamin D metabolising system 24-hydroxylase (CYP24A1) |
| title | 25-Hydroxycholecalciferol Inhibits Cell Growth and Induces Apoptosis in SiHa Cervical Cells via Autocrine Vitamin D Metabolism |
| title_full | 25-Hydroxycholecalciferol Inhibits Cell Growth and Induces Apoptosis in SiHa Cervical Cells via Autocrine Vitamin D Metabolism |
| title_fullStr | 25-Hydroxycholecalciferol Inhibits Cell Growth and Induces Apoptosis in SiHa Cervical Cells via Autocrine Vitamin D Metabolism |
| title_full_unstemmed | 25-Hydroxycholecalciferol Inhibits Cell Growth and Induces Apoptosis in SiHa Cervical Cells via Autocrine Vitamin D Metabolism |
| title_short | 25-Hydroxycholecalciferol Inhibits Cell Growth and Induces Apoptosis in SiHa Cervical Cells via Autocrine Vitamin D Metabolism |
| title_sort | 25 hydroxycholecalciferol inhibits cell growth and induces apoptosis in siha cervical cells via autocrine vitamin d metabolism |
| topic | cervical cancer SiHa 25-hydroxycholecalciferol apoptosis vitamin D metabolising system 24-hydroxylase (CYP24A1) |
| url | https://www.mdpi.com/2227-9059/11/3/871 |
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