Vitamin D and its analogs as anticancer and anti-inflammatory agents

Chen, Jingxuan; Tang, Ziyu; Słomiński, Andrzej; Li, Wei; Żmijewski, Michał A.; Liu, Yao

doi:10.1016/j.ejmech.2020.112738

Cited by 65 publications

(56 citation statements)

References 116 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In this study, we investigated the effects of a chronic inflammatory stimulus on two models of pancreatic cancer, and we described the impact of vitamin D and the relevance of TGFβ metabolic activity on cancer progression. Vitamin D shows differentiating and anti-inflammatory properties [38,39], and its efficacy on cancer could depend on its influence on TGFβ signaling. We chose pancreatic cancer as the target of our analysis for several reasons.…”

Section: Discussionmentioning

confidence: 99%

TGF Beta Induces Vitamin D Receptor and Modulates Mitochondrial Activity of Human Pancreatic Cancer Cells

Fiz

Apprato

Ricca

et al. 2021

Cancers

View full text Add to dashboard Cite

The inflammatory cytokine TGFβ is both a tumor suppressor during cancer initiation and a promoter of metastasis along cancer progression. Inflammation and cancer are strictly linked, and cancer onset often correlates with the insufficiency of vitamin D, known for its anti-inflammatory properties. In this study, we investigated the interplay between TGFβ and vitamin D in two models of human pancreatic cancer, and we analyzed the metabolic effects of a prolonged TGFβ treatment mimicking the inflammatory environment of pancreatic cancer in vivo. We confirmed the induction of the vitamin D receptor previously described in epithelial cells, but the inhibitory effects of vitamin D on epithelial–mesenchymal transition (EMT) were lost when the hormone was given after a long treatment with TGFβ. Moreover, we detected an ROS-mediated toxicity of the acute treatment with TGFβ, whereas a chronic exposure to low doses had a protumorigenic effect. In fact, it boosted the mitochondrial respiration and cancer cell migration without ROS production and cytotoxicity. Our observations shed some light on the multifaceted role of TGFβ in tumor progression, revealing that a sustained exposure to TGFβ at low doses results in an irreversibly increased EMT associated with a metabolic modulation which favors the formation of metastasis.

show abstract

Section: Discussionmentioning

confidence: 99%

TGF Beta Induces Vitamin D Receptor and Modulates Mitochondrial Activity of Human Pancreatic Cancer Cells

Fiz

Apprato

Ricca

et al. 2021

Cancers

View full text Add to dashboard Cite

show abstract

“…Today, differentiation syndrome is well managed in APL, as well as in patient receiving IDH MUT inhibitors and treatment interruption is rarely considered [49,50]. Moreover, there is a large number of VD analogs already used in clinic which prevent VD-related hypercalcemia [48,51]. However, combination of treatments could still increase undesirable effects and toxicity.…”

Section: Discussionmentioning

confidence: 99%

Activation of Vitamin D Receptor Pathway Enhances Differentiating Capacity in Acute Myeloid Leukemia with Isocitrate Dehydrogenase Mutations

Sabatier

Boet

Zaghdoudi

et al. 2021

Cancers

View full text Add to dashboard Cite

Relapses and resistance to therapeutic agents are major barriers in the treatment of acute myeloid leukemia (AML) patients. These unfavorable outcomes emphasize the need for new strategies targeting drug-resistant cells. As IDH mutations are present in the preleukemic stem cells and systematically conserved at relapse, targeting IDH mutant cells could be essential to achieve a long-term remission in the IDH mutant AML subgroup. Here, using a panel of human AML cell lines and primary AML patient specimens harboring IDH mutations, we showed that the production of an oncometabolite (R)-2-HG by IDH mutant enzymes induces vitamin D receptor-related transcriptional changes, priming these AML cells to differentiate with pharmacological doses of ATRA and/or VD. This activation occurs in a CEBPα-dependent manner. Accordingly, our findings illuminate potent and cooperative effects of IDH mutations and the vitamin D receptor pathway on differentiation in AML, revealing a novel therapeutic approach easily transferable/immediately applicable to this subgroup of AML patients.

show abstract

“…Through this transcription factor, calcitriol exerts many anticancer effects, including growth inhibition, induction of cell differentiation, anti-inflammatory activity, cell cycle arrest, oncogenes downregulation, and many others that place calcitriol as a natural endogenous cancer-preventive antineoplastic factor [ 40 , 41 ]. This has been the basis of the vast number of studies designed to study calcitriol and its analogs as pharmacological options in the oncological setting [ 42 ]. Notably, calcitriol not only acts as an antineoplastic agent, but also can help to overcome drug resistance, increase the susceptibility to chemotherapy and even potentiate the effects of conventional chemotherapeutic agents and radiation therapy.…”

Section: Calcitriol In Combination With Chemo/radiotherapy In Bcmentioning

confidence: 99%

Combinations of Calcitriol with Anticancer Treatments for Breast Cancer: An Update

Segovia-Mendoza

García-Quiroz

Díaz

et al. 2021

IJMS

View full text Add to dashboard Cite

Preclinical, clinical, and epidemiological studies indicate that vitamin D3 (VD) deficiency is a risk factor for the development of breast cancer. Underlying mechanisms include the ability of calcitriol to induce cell differentiation, inhibit oncogenes expression, and modify different signaling pathways involved in the control of cell proliferation. In addition, calcitriol combined with different kinds of antineoplastic drugs has been demonstrated to enhance their beneficial effects in an additive or synergistic fashion. However, a recognized adjuvant regimen based on calcitriol for treating patients with breast cancer has not yet been fully established. Accordingly, in the present work, we review and discuss the preclinical and clinical studies about the combination of calcitriol with different oncological drugs, aiming to emphasize its main therapeutic benefits and opportunities for the treatment of this pathology.

show abstract

Vitamin D and its analogs as anticancer and anti-inflammatory agents

Cited by 65 publications

References 116 publications

TGF Beta Induces Vitamin D Receptor and Modulates Mitochondrial Activity of Human Pancreatic Cancer Cells

TGF Beta Induces Vitamin D Receptor and Modulates Mitochondrial Activity of Human Pancreatic Cancer Cells

Activation of Vitamin D Receptor Pathway Enhances Differentiating Capacity in Acute Myeloid Leukemia with Isocitrate Dehydrogenase Mutations

Combinations of Calcitriol with Anticancer Treatments for Breast Cancer: An Update

Contact Info

Product

Resources

About