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Vitamin D decreases tumor cell growth and invasiveness in primary malignant bone tumors in vitro

Published on Thursday, 20 August 2026

Abstract

Primary malignant bone tumors (PMBTs) are rare neoplasms arising from bone tissue. Limited evidence suggests an association between reduced serum 25(OH) vitamin D3 levels and PMBT incidence.

The active metabolite 1,25(OH)2 vitamin D3 (1,25D3) modulates tumor cell proliferation, apoptosis, and migration through interactions with the vitamin D receptor (VDR).

This study investigated the effects of 1,25D3 on osteosarcoma (MG-63, SaOS-2), chondrosarcoma (SW-1353), and Ewing's sarcoma (RD-ES) cell lines.

Expression of key components of vitamin D metabolism, including 1α-hydroxylase (CYP27B1), 24-hydroxylase (CYP24A1), VDR, protein disulfide-isomerase A3 (PDIA3), and the 1,25D3-responsive bone gamma-carboxyglutamate protein (BGLAP), was analyzed at mRNA and protein levels. VDR nuclear translocation was assessed by Western blotting. Cell viability, cell cycle progression, apoptosis, and migration were evaluated using metabolic assays, flow cytometry, immunocytochemistry, wound healing, and live-cell imaging.

Treatment with 1,25D3 upregulated CYP24A1 in osteosarcoma cells, while BGLAP expression was detected in both osteosarcoma and SW-1353 cells. All examined cell lines expressed VDR and PDIA3, and 1,25D3 induced VDR nuclear translocation. MG-63 cell viability decreased by 23%, whereas SW-1353 cell viability decreased by 10%, with no significant changes observed in SaOS-2 and RD-ES cells. In MG-63 cells, 1,25D3 induced a significant accumulation of cells in the G1 phase, consistent with cell-cycle arrest, whereas only minor cell-cycle alterations were observed in the other cell lines.

Interestingly, 1,25D3 reduced the proportion of apoptotic osteosarcoma cells by 18-30%.

The migration of MG-63 cells was significantly reduced by 1,25D3, and an inhibitory trend, albeit not statistically significant, was also observed in RD-ES cells.

In conclusion, 1,25D3 modulated cell viability, apoptosis, and migration in PMBT cell models, with distinct, cell-type-specific responses. These findings suggest a potential role for 1,25D3 in regulating PMBT growth and invasiveness.

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About this publication.

The Di Bella's Method: Use of Vitamin D, Melatonin (since 1974), Somatostatin/Octreotide analogues and/or derivatives (since 1977), Retinoids (40mg per day Beta-Carotene, 10mg per day ATRA and 10mg per day Axerophthol palmitate), Melatonin (since 1974), Vitamin D, Cabergoline and/or Bromocriptine with pseudo-Metronomic Chemotherapy Cyclophosphamide and/or Hydroxyurea (together with others chemical compounds) in Fibro/Osteo-Sarcoma (the dosage and administration schedule must be individualised for each patient):

- A retrospective observational study on cases of Osteosarcomas treated with a multitherapy: The rationale and effectiveness;

- A Retrospective Observational Study on Cases of Sarcoma Treated with the Di Bella Method: Rationale and Effectiveness;

- Congenital fibrosarcoma in complete remission with Somatostatin, Retinoids, Vitamin D3, Vitamin E, Vitamin C, Melatonin, Calcium, Chondroitin sulfate associated with low doses of Cyclophosphamide in a 14-year Follow Up;

- The Di Bella Method (A Fixed Part - Dihydrotachysterol, Alfacalcidol, synthetic Vitamin D3 - Preferably the blood concentration value should be around the middle between 75ng/ml and 100ng/ml);

- Vitamin D (analogues and/or derivatives) and cancer - In vitro, review and in vivo publications;

- The Di Bella Method (A Fixed Part - All-Trans Retinoic Acid, Analogues and/or Derivatives - Approximately 60mg per day orally: 40mg per day Beta-Carotene/β-Carotene, 10mg per day ATRA and 10mg per day Axerophthol palmitate);

- All-Trans-Retinoic Acid (ATRA - analogues and/or derivatives) - In vitro, review and in vivo publications;

- Solution of retinoids in vitamin E in the Di Bella Method biological multitherapy;

- The Di Bella Method (A Fixed Part - Alpha tocopheryl acetate/Vitamin E, approximately 20 grams per day orally);

- Cancer and Vitamin E (analogues and/or derivatives) and cancer - In vitro, review and in vivo publications;

- The Di Bella Method (A Fixed Part - Cyclophosphamide 50mg tablets and/or Hydroxyurea 500mg tablets, one or two per day);

- The Di Bella Method (A Fixed Part - Calcium, 2 grams per day, orally);

- The Di Bella Method (A Fixed Part - Somatostatin, Octreotide, Sandostatin LAR, analogues and/or derivatives since 1977);

- Somatostatin in oncology, the overlooked evidences - In vitro, review and in vivo publications;

- Publication, 2018 Jul: Over-Expression of GH/GHR in Breast Cancer and Oncosuppressor Role of Somatostatin as a Physiological Inhibitor (from Di Bella's Foundation);

- Publication, 2018 Sep: The over-expression of GH/GHR in tumour tissues with respect to healthy ones confirms its oncogenic role and the consequent oncosuppressor role of its physiological inhibitor, somatostatin: a review of the literature (from Di Bella's Foundation);

- Publication, 2019 Aug: The Entrapment of Somatostatin in a Lipid Formulation: Retarded Release and Free Radical Reactivity (from Di Bella's Foundation);

- Publication, 2019 Sep: Effects of Somatostatin and Vitamin C on the Fatty Acid Profile of Breast Cancer Cell Membranes (from Di Bella's Foundation);

- Publication, 2019 Sep: Effects of somatostatin, curcumin, and quercetin on the fatty acid profile of breast cancer cell membranes (from Di Bella's Foundation);

- Publication, 2020 Sep: Two neuroendocrine G protein-coupled receptor molecules, somatostatin and melatonin: Physiology of signal transduction and therapeutic perspectives (from Di Bella's Foundation);

- The Di Bella Method (A Fixed Part - Bromocriptine and/or Cabergoline);

- Prolactin inhibitors in oncology - In vitro, review and in vivo publications;

The Di Bella's Method: Use of Vitamin D analogues and/or derivatives - together with others chemical compounds: the dosage and administration schedule must be individualised for each patient - in several Oncological Pathologies:

- A retrospective observational clinical study of triple negative breast cancer cases treated with Di Bella Method: A preliminary data;

- The Synergism of Somatostatin, Melatonin, Vitamins Prolactin and Estrogen Inhibitors Increased Survival, Objective Response and Performance Status In 297 Cases of Breast Cancer;

- Complete objective response, stable for 5 years, with the Di Bella Method, of multiple-metastatic carcinoma of the breast;

- Evaluation of the safety and efficacy of the first-line treatment with somatostatin combined with melatonin, retinoids, vitamin D3, and low doses of cyclophosphamide in 20 cases of breast cancer: a preliminary report;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 122 cases of breast cancer;

- Complete objective response to biological therapy of plurifocal breast carcinoma;

- A retrospective observational study on cases of anaplastic brain tumors treated with the Di Bella Method: A rationale and effectiveness;

- Recurrent Glioblastoma Multiforme (grade IV – WHO 2007): a case of complete objective response achieved by means of the concomitant administration of Somatostatin and Octreotide – Retinoids – Vitamin E – Vitamin D3 – Vitamin C – Melatonin – D2 R agonists (Di Bella Method – DBM) associated with Temozolomide;

- The Di Bella Method DBM improved survival objective response and performance status in a retrospective observational clinical study on 23 tumours of the head and neck;

- Chronic Lymphocytic Leukemia: Long-Lasting Remission with Combination of Cyclophosphamide, Somatostatin, Bromocriptine, Retinoids, Melatonin, and ACTH;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in advanced non-small-cell lung cancer patients with low performance status;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in chemotherapy-pretreated patients with advanced lung adenocarcinoma and low performance status;