The alkynylphosphonate analogue of calcitriol EM1 has potent anti-metastatic effects in breast cancer

Ferronato, María Julia; Obiol, Diego Javier; Fermento, María Eugenia; Gandini, Norberto Ariel; Alonso, Ernesto; Salomón, Débora Gisele; Vitale, Cristian; Mascaró, Evangelina; Fall, Yagamare; Raimondi, Ana R.; Curino, Alejandro Carlos; Facchinetti, María Marta

doi:10.1016/j.jsbmb.2015.09.009

Cited by 13 publications

(8 citation statements)

References 44 publications

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“…HCT116 cells (2.5 x 10 5 ) were seeded onto sterile 35 mm plates and allowed to grow until a confluent cell monolayer was formed. Wound healing assay was performed as previously described [17]. Cells were scratched with 200 µl pipette and then fresh medium containing UVB1, calcitriol or vehicle 100 nM was added to each plate.…”

Section: Wound-healing Assaymentioning

confidence: 99%

“…Immunofluorescence (IF) was performed as previously described [17]. Briefly, HCT116 cells were seeded on glass coverslips in 35 mm petri dishes and cultured until 50% confluence.…”

Section: Immunofluorescencementioning

confidence: 99%

“…Blood samples were collected from mice at the beginning and at the end of the experiments. Animals were anesthetized as described previously [17] and capillary tubes were used to collect blood from the retro-orbital sinus. Samples were held on ice, processed at 4°C, and plasma was separated and stored at -20°C until assayed.…”

Section: Blood Calcium Levelsmentioning

confidence: 99%

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The UVB1 Vitamin D analogue inhibits colorectal carcinoma progression

Ferronato

Alonso

Gandini

et al. 2016

The Journal of Steroid Biochemistry and Molecular Biology

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Vitamin D has been shown to display a wide variety of antitumour effects, but their therapeutic use is limited by its severe side effects. We have designed and synthesized a Gemini vitamin D analogue of calcitriol (UVB1) which has shown to display antineoplastic effects on different cancer cell lines without causing hypercalcemia. The aim of this work has been to investigate, by employing in silico, in vitro, and in vivo assays, whether UVB1 inhibits human colorectal carcinoma progression. We demonstrated that UVB1 induces apoptotic cell death and retards cellular migration and invasion of HCT116 colorectal carcinoma cells. Moreover, the analogue reduced the tumour volume in vivo, and modulated the expression of Bax, E-cadherin and nuclear β-catenin in tumour animal tissues without producing toxic effects. In silico analysis showed that UVB1 exhibits greater affinity for the ligand binding domain of vitamin D receptor than calcitriol, and that several characteristics in the three-dimensional conformation of VDR may influence the biological effects. These results demonstrate that the Gemini vitamin D analogue affects the growth of the colorectal cancer and suggest that UVB1 is a potential chemotherapeutic agent for treatment of this disease.

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Section: Wound-healing Assaymentioning

confidence: 99%

“…Immunofluorescence (IF) was performed as previously described [17]. Briefly, HCT116 cells were seeded on glass coverslips in 35 mm petri dishes and cultured until 50% confluence.…”

Section: Immunofluorescencementioning

confidence: 99%

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The UVB1 Vitamin D analogue inhibits colorectal carcinoma progression

Ferronato

Alonso

Gandini

et al. 2016

The Journal of Steroid Biochemistry and Molecular Biology

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“…When its active metabolite, calcitriol, is used with freezing of prostate cancer cells, freeze sensitivity increased to nadir temperatures as high as À5 C to À15 C regardless of the androgen sensitivity or rate of division (Ki67) of the prostate cancer [39][40][41][42]. This response is like other cancer types which carry the VD3 receptor such as breast [43][44][45], lung [46], colon [47,48] and pancreas [49] in addition to prostate ( Figure 4) [39][40][41][42]. The use of calcitriol as an adjunct as well as the VD3 receptor hypothesis is currently being tested in other cancers which do not contain the VD3 receptor, including bladder and liver cancer.…”

Section: Nutraceuticalsmentioning

confidence: 98%

Cryoablation: physical and molecular basis with putative immunological consequences

Baust

Snyder

Santucci

et al. 2019

International Journal of Hyperthermia

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Cryoablation (CA) is unique as the singular energy deprivation therapy that impacts all cellular processes. CA is independent of cell cycle stage and degree of cellular stemness. Importantly, CA is typically applied as a non-repetitive (single session) treatment that does not support adaptative mutagenesis as do many repetitive therapies. CA is characterized by the launch of multiple forms of cell death including (a) ice-related physical damage, (b) initiation of cellular stress responses (kill switch activation) and launch of necrosis and apoptosis, (c) vascular stasis, and (d) likely activation of ablative immune responses. CA is not without limitation related to the thermal gradient formed between cryoprobe surface ($À185 C) and the distal surface of the freeze zone ($0 C) requiring freeze margin extension beyond the tumor boundary (up to $1 cm). This limitation is mitigated in part by commonly applied dual freeze thaw cycles and the use of freeze sensitizing adjuvants. This review will (1) identify the cascade of damaging effects of the freeze-thaw process, its physical and molecular-based relationships, (2) a likely immunological involvement (abscopic effect), and (3) explore the use of freeze-sensitizing adjuvants necessary to limit freezing beyond the tumor margin.

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“…Immunofluorescence was performed as previously described [10]. Briefly, LM3 cells were seeded on glass coverslips (9x10 4 were calculated by a correction with total protein content of the sample and measured using a COBAS C311 analyzer (Roche Diagnostics).…”

Section: Actin Cytoskeleton Analysis By Rhodamine-phalloidin Stainingmentioning

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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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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The alkynylphosphonate analogue of calcitriol EM1 has potent anti-metastatic effects in breast cancer

Cited by 13 publications

References 44 publications

The UVB1 Vitamin D analogue inhibits colorectal carcinoma progression

The UVB1 Vitamin D analogue inhibits colorectal carcinoma progression

Cryoablation: physical and molecular basis with putative immunological consequences

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

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