Antitumoral effects of the alkynylphosphonate analogue of calcitriol EM1 on glioblastoma multiforme cells

Ferronato, María Julia; Alonso, Ernesto; Salomón, Débora Gisele; Fermento, María Eugenia; Gandini, Norberto Ariel; Quevedo, Mario Alfredo; Mascaró, Evangelina; Vitale, Cristian; Fall, Yagamare; Facchinetti, María Marta; Curino, Alejandro Carlos

doi:10.1016/j.jsbmb.2017.10.019

Cited by 15 publications

(22 citation statements)

References 71 publications

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“…presents the corresponding energies for each interaction component for calcitriol and ML-344 at both pH values.From the analysis of calcitriol component, no significant differences were observed regarding the affinity for VDR at both pH values. In agreement with our previous reports[30,34], the binding of calcitriol at both pHs is mainly stabilizedby Van der Waals interactions (-60.1 and -63.5 Kcal/mol at pH 5.5 and 7, respectively), with a lesser contribution of the EEL component (-33.2 and -27.2…”

supporting

confidence: 93%

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Synthesis of a novel analog of calcitriol and its biological evaluation as antitumor agent

Ferronato

Obiol

Alonso

et al. 2019

The Journal of Steroid Biochemistry and Molecular Biology

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Calcitriol analogs have shown promising potential as compounds to be used in cancer chemotherapy. This report presents the synthesis of a novel vitamin D derivative with an amide and a carboxyl group in its side chain, called ML-344. In addition, we report its in vitro antitumor activity and its in vivo calcemic effects. We demonstrate that the analog decreases cell viability and retards cell migration of different breast, glioblastoma and head and neck cancer cell lines. Additionally, unlike calcitriol, ML-344 does not display citotoxicity to the murine non-malignant mammary cells and human astrocytes. In concordance with the antimigratory effects found in breast cancer cells, ML-344 decreased the invasive capacity and induced a rearrangement of the actin cytoskeleton in the LM3 breast cancer cell line. In relation to the in vivo studies, the analog did not cause hypercalcemic effects in CF1 mice administered daily at 5 μg/Kg of body weight during a period of 264 h. Finally, computational studies were performed to evaluate the potential binding of the analog to the vitamin D receptor and the in silico assays showed that ML-344 is able to bind to VDR with interesting particularities and greater affinity than calcitriol. Altogether, these results suggest that ML-344 has a promising potential as an antitumor agent with a differential effect between tumor and non-malignant cells.

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confidence: 93%

“…non-malignant cells such as astrocytes [30] and HC11 cell line [31], we also decided to evaluate the effect of the analog on these cells.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Synthesis of a novel analog of calcitriol and its biological evaluation as antitumor agent

Ferronato

Obiol

Alonso

et al. 2019

The Journal of Steroid Biochemistry and Molecular Biology

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“…A number of experimental vitamin D analogues have been synthesized and described in the literature . Potential problems in developing this type of compounds for clinical use include the risk of systemic side effects, particularly on calcium homoeostasis.…”

Section: Discussionmentioning

confidence: 99%

“…The strongest inhibition of migration was observed with 1a,25(OH) 2 D 3 , but both tacalcitol and calcipotriol significantly inhibited migration by about 50% compared to control. A number of experimental vitamin D analogues have been synthesized and described in the literature [20,42]. Potential problems in developing this type of compounds for clinical use include the risk of systemic side effects, particularly on calcium homoeostasis.…”

Section: Discussionmentioning

confidence: 99%

Vitamin D Analogues Tacalcitol and Calcipotriol Inhibit Proliferation and Migration of T98G Human Glioblastoma Cells

Emanuelsson

Wikvall

Friman

et al. 2018

Basic Clin Pharma Tox

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The active form of vitamin D (1α,25-dihydroxyvitamin D) acts as a steroid hormone and binds to the vitamin D receptor. This receptor is expressed in most cell types including cells in the central nervous system (CNS). Vitamin D has several functions in the body including effects on brain development, neuroprotection and immunological regulation. It has been shown that vitamin D has antiproliferative activities in different cancer cell lines. Tacalcitol and calcipotriol are synthetic analogues of 1α,25-dihydroxyvitamin D with reduced effect on calcium metabolism. The aim of this study was to analyse the effects of tacalcitol and calcipotriol on cell viability, proliferation and migration in the human glioblastoma cell line T98G. Glioblastoma is the most lethal type of primary tumours in the CNS. Both analogues decreased cell viability and/or growth, dose-dependently, in concentrations between 1 nM and 10 μM. Manual counting indicated suppressive effects by the vitamin D analogues on proliferation. Treatment with tacalcitol strongly suppressed thymidine incorporation, indicating that the vitamin D analogues mainly inhibit proliferation. Also, effects on cell migration were measured with wound-healing assay. Both calcipotriol and tacalcitol reduced the migration rate of T98G cells compared to vehicle-treated cells. However, they had no effect on caspase-3 and -7 activities, suggesting that their mechanism of action does not involve induction of apoptosis. The current results indicate that the vitamin D analogues tacalcitol and calcipotriol strongly reduce proliferation and migration of human glioblastoma T98G cells, suggesting a potential role for this type of compounds in treatment of brain cancer.

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“…A propriedade antiproliferativa da VD estaria relacionada com a regulação positiva transcricional de genes inibidores de quinase dependente de ciclina (CDK) como a TP21 e TP27, e diminuição da expressão gênica de ciclina, (Fleet et al 2012;Salomo'n et al 2014;Ferronato et al 2018). Adicionalmente, a inibição da expressão da proteína RB também parece estar envolvida, propiciando a parada do ciclo celular nas fases G0/G1, repressão da transcrição gênica do proto-oncogene MYC que está relacionado com a síntese de fatores de transcrição (Feldman et al, 2014…”

Section: Mecanismo De Ação E a Relação Entre A Vd E A Carcinogêneseunclassified

Prevalência De Hepatites Virais Em Municípios Da Amazônia Legal

Santos¹,

Brune²,

Riegel³

et al. 2020

Ciências Da Saúde No Brasil: Impasses E Desafios 7

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Antitumoral effects of the alkynylphosphonate analogue of calcitriol EM1 on glioblastoma multiforme cells

Cited by 15 publications

References 71 publications

Synthesis of a novel analog of calcitriol and its biological evaluation as antitumor agent

Synthesis of a novel analog of calcitriol and its biological evaluation as antitumor agent

Vitamin D Analogues Tacalcitol and Calcipotriol Inhibit Proliferation and Migration of T98G Human Glioblastoma Cells

Prevalência De Hepatites Virais Em Municípios Da Amazônia Legal

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