Effect of Vitamin D on Paclitaxel Efficacy in Triple-negative Breast Cancer Cell Lines

Wilhelm, Catherine A.; Clor, Zackary J.; Kelts, Jessica L.

doi:10.21873/anticanres.12823

Cited by 10 publications

(10 citation statements)

References 21 publications

(26 reference statements)

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“…Paclitaxel (PTX), a taxane, belongs to the most widely used anticancer drugs and is often applied in front-line chemotherapy in breast cancer in combination with anthracyclines or platinum chemotherapeutic drugs (reviewed in [116]). Wilhelm et al, showed that 1,25(OH)2D and 25(OH)D at low (up to 10 nM) concentrations increased the proliferation of the p53-wild type TNBC DU4475 cells and potentiated the cytotoxic action of PTX [117]. However, this effect was not observed in MDA-MB-231 cells that did not contain p53.…”

Section: Therapeutic Resistancementioning

confidence: 99%

Vitamin D in Triple-Negative and BRCA1-Deficient Breast Cancer—Implications for Pathogenesis and Therapy

Błasiak

Pawłowska

Chojnacki

et al. 2020

IJMS

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Several studies show that triple-negative breast cancer (TNBC) patients have the lowest vitamin D concentration among all breast cancer types, suggesting that this vitamin may induce a protective effect against TNBC. This effect of the active metabolite of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D), can be attributed to its potential to modulate proliferation, differentiation, apoptosis, inflammation, angiogenesis, invasion and metastasis and is supported by many in vitro and animal studies, but its exact mechanism is poorly known. In a fraction of TNBCs that harbor mutations that cause the loss of function of the DNA repair-associated breast cancer type 1 susceptibility (BRCA1) gene, 1,25(OH)2D may induce protective effects by activating its receptor and inactivating cathepsin L-mediated degradation of tumor protein P53 binding protein 1 (TP53BP1), preventing deficiency in DNA double-strand break repair and contributing to genome stability. Similar effects can be induced by the interaction of 1,25(OH)2D with proteins of the growth arrest and DNA damage-inducible 45 (GADD45) family. Further studies on TNBC cell lines with exact molecular characteristics and clinical trials with well-defined cases are needed to determine the mechanism of action of vitamin D in TNBC to assess its preventive and therapeutic potential.

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Section: Therapeutic Resistancementioning

confidence: 99%

Vitamin D in Triple-Negative and BRCA1-Deficient Breast Cancer—Implications for Pathogenesis and Therapy

Błasiak

Pawłowska

Chojnacki

et al. 2020

IJMS

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“…One flask was used as a control group, and the other five were given docetaxel at the above concentrations. The concentrations were determined by similar corresponding experimental procedures reported in the literature [ 19 ]. The cells were then rinsed with PBS to remove dead cells, and the PBS was aspirated with a glass pipette.…”

Section: Methodsmentioning

confidence: 99%

In Vitro and In Vivo Effects of Docetaxel and Dasatinib in Triple-Negative Breast Cancer: A Research Study

Passos,

Papadimitriou,

Katsouda

et al. 2023

Cureus

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Introduction Triple-negative breast cancer (TNBC) comprises a heterogeneous group of tumors with a single trait in common: an evident aggressive nature with higher rates of relapse and lower overall survival in the metastatic context when compared to other subtypes of breast cancer. To date, not a single targeted therapy has been approved for the treatment of TNBC, and cytotoxic chemotherapy remains the standard treatment. In the present experimental study, we examine the effects of the chemotherapeutic docetaxel and the bcr/abl kinase inhibitor dasatinib on TNBC cell lines (in vitro) and on TNBC tumor xenograft mouse models (in vivo). Materials and methods TNBC cell lines were cultivated and treated with various concentrations of docetaxel and dasatinib (5 nM to 100 nM). Cell death and apoptosis were studied by flow cytometry. TNBC cell lines were then injected in BALB/c athymic nude mice to express the tumor in vivo. Four groups of mice were created (group A: control; group B: DOC; group C: DAS; group D: DOC + DAS) and treated, respectively, with the drugs and their combination. Tumors were obtained, maintained in a 10% formaldehyde solution, embedded in paraffin, and sent for further histological evaluation (hematoxylin-eosin staining and immune-histochemical analysis) to assess the tumor growth inhibition. Results The cytotoxic effects of docetaxel seem statistically important, with little effect on apoptosis. The effect of dasatinib in vitro and vivo is statistically important, in terms of apoptosis and tumor reduction, with little adverse effects. Conclusions TNBC is a difficult-to-treat oncologic condition, even in an experimental setting. Promising results concerning the addition of targeted therapies (dasatinib) to the conventional cytotoxic ones (docetaxel) have been shown, awaiting further evaluation.

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“…Noteworthy, the co-treatment was more effective in ER-positive cells compared to TNBC cells. However, and very interesting, Wilhelm and colleagues showed that the effect of calcitriol or its precursor calcidiol on paclitaxel efficacy differed within the TNBC subtypes and depended on p53-positivity and VDR status [ 53 ].…”

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

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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.

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Effect of Vitamin D on Paclitaxel Efficacy in Triple-negative Breast Cancer Cell Lines

Abstract: The effect of vitamin D on DU4475 cell viability was different than in other TNBC cells. The effect of PTX on DU4475 cells was enhanced with vitamin D. MDA-MB-231 cells were relatively resistant to the effects of PTX.

Cited by 10 publications

References 21 publications

Vitamin D in Triple-Negative and BRCA1-Deficient Breast Cancer—Implications for Pathogenesis and Therapy

Vitamin D in Triple-Negative and BRCA1-Deficient Breast Cancer—Implications for Pathogenesis and Therapy

In Vitro and In Vivo Effects of Docetaxel and Dasatinib in Triple-Negative Breast Cancer: A Research Study

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

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