Vitamin D Represses the Aggressive Potential of Osteosarcoma

Tahbazlahafi, Behnoosh; Paknejad, Mojgan; Khaghani, Shahnaz; Sadegh-Nejadi, Sahar; Khalili, Ehsan

doi:10.2174/1871530320666200821155756

Cited by 7 publications

(4 citation statements)

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“…These antiproliferative effects of vitamin D on osteosarcoma cell lines were only recently confirmed in a different study (115). Moreover, recent findings suggest that 1,25D treatment of osteosarcoma cells results in decreased cell proliferation, migration an invasiveness, thus, reducing the aggressive potential of osteosarcoma cells (116). Furthermore, we have recently demonstrated that the VDR itself, and independent of its ligand has a critical function in controlling cancer cell behaviour in bone and cancer metastasis to bone (117,118).…”

Section: Vitamin D In Bone Oncologymentioning

confidence: 88%

The role of vitamin D and vitamin D deficiency in orthopaedics and traumatology—a narrative overview of the literature

Maier¹,

Weißenberger

Rudert

et al. 2021

Ann Transl Med

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Vitamin D is considered to play an important role in musculoskeletal health. It's classical function is the regulation of calcium and phosphate homeostasis, thus ensuring a balanced bone metabolism that is characterised by an equal amount of bone resorption and bone formation. In the past decades, a plethora of pre-clinical and clinical studies reporting on potential health-beneficial properties of vitamin D have emerged. Moreover, there is an abundance of reports highlighting vitamin D deficiency and insufficiency in patients with almost innumerable diseases. Further, it is estimated that more than one billion people globally are affected by insufficient vitamin D levels. As such, research on vitamin D has been particularly popular over the past years. In orthopaedics and traumatology, most studies describe favourable effects of vitamin D in general. However, the relative importance of vitamin D is oftentimes debated. In this narrative review of the literature, we consider first, the properties of vitamin D and how vitamin D, vitamin D deficiency and the vitamin D receptor (VDR) impact on musculoskeletal health. Secondly, we provide an overview of studies reporting the prevalence of vitamin D deficiency in traumatology and diverse orthopaedic diseases including bone oncology. Lastly, we emphasise recent findings and touch on future perspectives in vitamin D research.

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Section: Vitamin D In Bone Oncologymentioning

confidence: 88%

The role of vitamin D and vitamin D deficiency in orthopaedics and traumatology—a narrative overview of the literature

Maier¹,

Weißenberger

Rudert

et al. 2021

Ann Transl Med

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“…VD3 and its analogs, such as osteosarcoma cell lines MG-63 and SaOS2, also promote osteoblast differentiation. P73 is essential for VD3-mediated osteosarcoma differentiation, and induction of p73 in response to DNA damage enhances VD3-mediated osteosarcoma cell line differentiation [ 115 , 116 , 117 , 118 , 119 , 120 ].…”

Section: Multiple Myeloma (Mm) and Osteosarcomamentioning

confidence: 99%

Research Progress of Natural Small-Molecule Compounds Related to Tumor Differentiation

Liu

Sun

2022

Molecules

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Tumor differentiation is a therapeutic strategy aimed at reactivating the endogenous differentiation program of cancer cells and inducing cancer cells to mature and differentiate into other types of cells. It has been found that a variety of natural small-molecule drugs can induce tumor cell differentiation both in vitro and in vivo. Relevant molecules involved in the differentiation process may be potential therapeutic targets for tumor cells. Compared with synthetic drugs, natural small-molecule antitumor compounds have the characteristics of wide sources, structural diversity and low toxicity. In addition, natural drugs with structural modification and transformation have relatively concentrated targets and enhanced efficacy. Therefore, using natural small-molecule compounds to induce malignant cell differentiation represents a more targeted and potential low-toxicity means of tumor treatment. In this review, we focus on natural small-molecule compounds that induce differentiation of myeloid leukemia cells, osteoblasts and other malignant cells into functional cells by regulating signaling pathways and the expression of specific genes. We provide a reference for the subsequent development of natural small molecules for antitumor applications and promote the development of differentiation therapy.

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“…25(OH)D is further hydroxylated in the kidneys or within specialized cell types by 25(OH)D-1-OHase (CYP27B1) to produce 1-alpha, 25-dihydroxyvitamin D (also known as 1,25(OH)2D), the biologically active derivative of vitamin D 29,[39][40][41][42][43] . The 1,25(OH)2D effects are mediated by the vitamin D receptor (VDR), an intracellular nuclear receptor superfamily member, that can promote cell cycle arrest and apoptosis via post-transcriptional and gene regulatory means 39,[44][45][46][47][48][49][50][51][52][53][54] . In mammals, the physiological and molecular effects of vitamin D3 on bone health and function have been experimentally and clinically validated 29 .…”

Section: Introductionmentioning

confidence: 99%

Vitamin D inhibits osteosarcoma by reprogramming nonsense-mediated RNA decay and SNAI2-mediated epithelial-to-mesenchymal transition

Capobianco

McGaughey

Seraphin

et al. 2023

Preprint

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Osteosarcomas are immune-resistant and metastatic in part due to an increase in nonsense-mediated RNA decay (NMD), reactive oxygen species (ROS), and epithelial-to-mesenchymal transition (EMT) induction. In this study, we examined the impact of vitamin D3 and its receptor (VDR) on the NMD-ROS-EMT signaling axis in osteosarcoma cells and spheroids, as well as wound-induced cell migration and osteosarcoma metastasis in vivo models. Activated VDR signaling enriched the EMT pathway in gene set enrichment analysis, whereas the active vitamin D3 metabolite, 1,25(OH)2D, inhibited EMT in osteosarcoma subtypes. Because EMT processes in cancer and tissue wounds are similar, experimentally induced EMT of mouse hair follicle stem cells revealed that Vdr signaling restricts cell migration during cutaneous wound healing. In osteosarcoma cells, ligand bound VDR inhibited EMT by interacting directly with and downregulating the EMT inducer SNAI2. Differential epigenetic regulation of SNAI2 and VDR distinguished highly metastatic from low metastatic osteosarcoma subtypes and responsiveness to 1,25(OH)2D. Furthermore, epigenome-wide motif and putative target gene analysis revealed the integration of the VDR with the NMD tumor immunogenic pathway. In an autoregulatory manner, 1,25(OH)2D inhibited NMD machinery genes, while simultaneously inducing the overexpression of known NMD target genes involved in tumor immune recognition and cell-to-cell adhesion. Dicer substrate siRNA knockdown of SNAI2 revealed superoxide dismutase 2 (SOD2)-mediated antioxidative responses and 1,25(OH)2D sensitization, which involves the non-canonical SOD2 nuclear-to-mitochondrial translocalization and inhibition of ROS. Calcipotriol, a clinically relevant non-calcemic vitamin D3 derivative, inhibited osteosarcoma metastasis in a mouse xenograft model. Our research reveals novel vitamin D3 and calcipotriol osteosarcoma-inhibiting processes.

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Vitamin D Represses the Aggressive Potential of Osteosarcoma

Cited by 7 publications

References 0 publications

The role of vitamin D and vitamin D deficiency in orthopaedics and traumatology—a narrative overview of the literature

The role of vitamin D and vitamin D deficiency in orthopaedics and traumatology—a narrative overview of the literature

Research Progress of Natural Small-Molecule Compounds Related to Tumor Differentiation

Vitamin D inhibits osteosarcoma by reprogramming nonsense-mediated RNA decay and SNAI2-mediated epithelial-to-mesenchymal transition

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