25-Hydroxycholecalciferol inhibits cell growth and induces apoptosis in SiHa cervical cells via autocrine vitamin D metabolism

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Authors

Punchoo, Rivak
Dreyer, Greta
Pillay, Tahir S.

Journal Title

Journal ISSN

Volume Title

Publisher

MDPI

Abstract

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.

Description

DATA AVAILABILITY STATEMENT : The study data can be made available upon request to the corresponding author. The data presented in this study are available upon request from the corresponding author. The data are not publicly available due to the institutional restrictions regarding the current data submission and findings for degree purposes.

Keywords

Cervical cancer, SiHa, 25-hydroxycholecalciferol, Apoptosis, 24-hydroxylase (CYP24A1), 1-Alpha hydroxylase (CYP27B1), Vitamin D receptor (VDR), SDG-03: Good health and well-being, Vitamin D metabolising system (VDMS)

Sustainable Development Goals

SDG-03:Good heatlh and well-being

Citation

Punchoo, R.; Dreyer, G.; Pillay, T.S. 25-Hydroxycholecalciferol Inhibits Cell Growth and Induces Apoptosis in SiHa Cervical Cells via Autocrine Vitamin D Metabolism. Biomedicines 2023, 11, 871. https://doi.org/10.3390/biomedicines11030871.