Vitamin D metabolism in cancer: potential feasibility of vitamin D metabolism blocking therapy

Kamiya, Sakura; Nakamori, Yuna; Takasawa, Akira; Takasawa, Kumi; Kyuno, Daisuke; Ono, Yoshio; Magara, Kazufumi; Osanai, Makoto

doi:10.1007/s00795-023-00348-x

Cited by 3 publications

(4 citation statements)

References 51 publications

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“…Importantly, we also noticed the upregulation of the VDR and a slight downregulation of CYP24A1 protein level in melanoma cells simultaneously treated with 1,25(OH) 2 D 3 and CPL304110 compared to monotreatment with the novel FGFRs inhibitor. It seems that in the experimental conditions used, catabolism of vitamin D by CYP24A1, the 24-hydroxylase, which is downstream effector of VDR responsible for 1,25(OH) 2 D 3 final deactivation [ 27 ], is decreased.…”

Section: Discussionmentioning

confidence: 99%

“…Through its involvement in inhibition of tumour cell proliferation, sensitisation to apoptosis and chemotherapy, and induction of cell differentiation or inhibition of epithelial-tomesenchymal transition, it exerts pleiotropic anticancer activities [25,27].…”

Section: Fgfr Inhibitors Efficiently Decrease Melanoma Cells' Viabili...mentioning

confidence: 99%

“…Although vitamin D is most widely known as a regulator of calcium and phosphate homeostasis in our body, it is appreciated that the role of this hormone is much more complex [ 24 , 25 , 26 ]. Through its involvement in inhibition of tumour cell proliferation, sensitisation to apoptosis and chemotherapy, and induction of cell differentiation or inhibition of epithelial-to-mesenchymal transition, it exerts pleiotropic anticancer activities [ 25 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

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Fibroblast Growth Factor Receptor Inhibitors Decrease Proliferation of Melanoma Cell Lines and Their Activity Is Modulated by Vitamin D

Piotrowska,

Nowak,

Wierzbicka

et al. 2024

IJMS

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Regardless of the unprecedented progress in malignant melanoma treatment strategies and clinical outcomes of patients during the last twelve years, this skin cancer remains the most lethal one. We have previously documented that vitamin D and its low-calcaemic analogues enhance the anticancer activity of drugs including a classic chemotherapeutic—dacarbazine—and an antiangiogenic VEGFRs inhibitor—cediranib. In this study, we explored the response of A375 and RPMI7951 melanoma lines to CPL304110 (CPL110), a novel selective inhibitor of fibroblast growth factor receptors (FGFRs), and compared its efficacy with that of AZD4547, the first-generation FGFRs selective inhibitor. We also tested whether 1,25(OH)2D3, the active form of vitamin D, modulates the response of the cells to these drugs. CPL304110 efficiently decreased the viability of melanoma cells in both A375 and RPMI7951 cell lines, with the IC50 value below 1 µM. However, the metastatic RPMI7951 melanoma cells were less sensitive to the tested drug than A375 cells, isolated from primary tumour site. Both tested FGFR inhibitors triggered G0/G1 cell cycle arrest in A375 melanoma cells and increased apoptotic/necrotic SubG1 fraction in RPMI7951 melanoma cells. 1,25(OH)2D3 modulated the efficacy of CPL304110, by decreasing the IC50 value by more than 4-fold in A375 cell line, but not in RPMI7951 cells. Further analysis revealed that both inhibitors impact vitamin D signalling to some extent, and this effect is cell line-specific. On the other hand, 1,25(OH)2D3, have an impact on the expression of FGFR receptors and phosphorylation (FGFR-Tyr653/654). Interestingly, 1,25(OH)2D3 and CPL304110 co-treatment resulted in activation of the ERK1/2 pathway in A375 cells. Our results strongly suggested possible crosstalk between vitamin D-activated pathways and activity of FGFR inhibitors, which should be considered in further clinical studies.

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Section: Discussionmentioning

confidence: 99%

Section: Fgfr Inhibitors Efficiently Decrease Melanoma Cells' Viabili...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Fibroblast Growth Factor Receptor Inhibitors Decrease Proliferation of Melanoma Cell Lines and Their Activity Is Modulated by Vitamin D

Piotrowska,

Nowak,

Wierzbicka

et al. 2024

IJMS

View full text Add to dashboard Cite

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“…In contrast, Lin et al [112] have found that the expression of CYP24A1 is inhibited by miR-1278 in CRC, which opens the possibility to increase miR-1278 expression to sensitize colon carcinoma cells to vitamin D compounds. Since augmented expression of CYP24A1 in CRC cells probably leads to depletion of intracellular 1,25(OH) 2 D 3 and therefore to the abolishment of its antitumor actions, combination therapy of vitamin D compounds with CYP24A1 inhibitors is worth exploring in CYP24A1-overexpressing tumors [113]. In this regard, H€ obaus et al [110] showed that 1,25(OH) 2 D 3 reduces proliferation of CRC cells overexpressing CYP24A1 only in the presence of the CYP24A1 inhibitor VID400.…”

Section: Expression Of Vitamin D Hydroxylases In Colorectal Cancermentioning

confidence: 99%

From molecular basis to clinical insights: a challenging future for the vitamin D endocrine system in colorectal cancer

Pereira,

Fernández‐Barral,

Larriba

et al. 2023

The FEBS Journal

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Colorectal cancer (CRC) is one of the most life‐threatening neoplasias in terms of incidence and mortality worldwide. Vitamin D deficiency has been associated with an increased risk of CRC. 1α,25‐dihydroxyvitamin D3 [1,25(OH)2D3], the most active vitamin D metabolite, is a pleiotropic hormone that, through its binding to a transcription factor of the nuclear receptor superfamily, is a major regulator of the human genome. 1,25(OH)2D3 acts on colon carcinoma and stromal cells and displays tumor protective actions. Here, we review the variety of molecular mechanisms underlying the effects of 1,25(OH)2D3 in CRC, which affect multiple processes that are dysregulated during tumor initiation and progression. Additionally, we discuss the epidemiological data that associate vitamin D deficiency and CRC, and the most relevant randomized controlled trials of vitamin D3 supplementation conducted in both healthy individuals and CRC patients.

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Nutritional Therapy Strategies Targeting Tumor Energy Metabolism

Chen,

2023

CDM

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Cancer is the second leading cause of mortality worldwide. The heightened nutrient uptake, particularly glucose, and elevated glycolysis observed in rapidly proliferating tumor cells highlight the potential targeting of energy metabolism pathways for the treatment of cancer. Numerous studies and clinical trials have demonstrated the efficacy of nutritional therapy in mitigating the adverse effects of chemotherapy and radiotherapy, enhancing treatment outcomes, prolonging survival, and improving the overall quality of life of patients. This review article comprehensively examines nutritional therapy strategies that specifically address tumor energy metabolism. Moreover, it explores the intricate interplay between energy metabolism and the gut microbiota in the context of nutritional therapy. The findings aim to provide valuable insights for future clinical research endeavors in this field.

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Vitamin D metabolism in cancer: potential feasibility of vitamin D metabolism blocking therapy

Cited by 3 publications

References 51 publications

Fibroblast Growth Factor Receptor Inhibitors Decrease Proliferation of Melanoma Cell Lines and Their Activity Is Modulated by Vitamin D

Fibroblast Growth Factor Receptor Inhibitors Decrease Proliferation of Melanoma Cell Lines and Their Activity Is Modulated by Vitamin D

From molecular basis to clinical insights: a challenging future for the vitamin D endocrine system in colorectal cancer

Nutritional Therapy Strategies Targeting Tumor Energy Metabolism

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