NEO212, a conjugate of temozolomide and perillyl alcohol, blocks the endothelial-to-mesenchymal transition in tumor-associated brain endothelial cells in glioblastoma

Marín-Ramos, Nagore I.; Jhaveri, Niyati; Thein, Thu Zan; Fayngor, Rochelle A.; Chen, Thomas C.; Hofman, Florence M.

doi:10.1016/j.canlet.2018.10.034

Cited by 23 publications

(16 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Histone-deacetylase HDAC inhibitor valproic acid, currently under clinical investigation for anticancer therapy, has recently been shown to induce EndoMT via a TGF- β 1 signaling pathway [15]. On the contrary, a conjugate of temozolomide and perillyl alcohol, used in a glioblastoma model, inhibits EndoMT and reverts the mesenchymal phenotype of tumor-associated brain EC [122]. Exposure to ionizing radiation also leads to a phenotypic conversion of EC in the colon and lung carcinoma preclinical models [57] but also in normal rectal tissues, leading then to radiation-induced fibrosis [49].…”

Section: Endomt and Response To Therapiesmentioning

confidence: 99%

Endothelial-to-Mesenchymal Transition (EndoMT): Roles in Tumorigenesis, Metastatic Extravasation and Therapy Resistance

Platel

Faure

Corre

et al. 2019

Journal of Oncology

View full text Add to dashboard Cite

Cancer cells evolve in a very complex tumor microenvironment, composed of several cell types, among which the endothelial cells are the major actors of the tumor angiogenesis. Today, these cells are also characterized for their plasticity, as endothelial cells have demonstrated their potential to modify their phenotype to differentiate into mesenchymal cells through the endothelial-to-mesenchymal transition (EndoMT). This cellular plasticity is mediated by various stimuli including transforming growth factor-β (TGF-β) and is modulated dependently of experimental conditions. Recently, emerging evidences have shown that EndoMT is involved in the development and dissemination of cancer and also in cancer cell to escape from therapeutic treatment. In this review, we summarize current updates on EndoMT and its main induction pathways. In addition, we discuss the role of EndoMT in tumorigenesis, metastasis, and its potential implication in cancer therapy resistance.

show abstract

Section: Endomt and Response To Therapiesmentioning

confidence: 99%

Endothelial-to-Mesenchymal Transition (EndoMT): Roles in Tumorigenesis, Metastatic Extravasation and Therapy Resistance

Platel

Faure

Corre

et al. 2019

Journal of Oncology

View full text Add to dashboard Cite

show abstract

“…Spironolactone, an aldosterone receptor-blocker, abrogates EndMT in a model of fibrosis, by blocking TGF-β and Notch signaling ( Chen et al, 2015 ). Notably, a derived-form of temozolomide, the standard chemotherapy in GBM, can suppress EndMT in tumor-associated ECs via the same mechanisms of TGF-β and Notch signaling inhibition ( Marin-Ramos et al, 2019 ), supporting the clinical value of this molecule.…”

Section: Targeting Of Endmtmentioning

confidence: 96%

“…Nevertheless, additional signals to TGF-βs may be required, as highlighted in a 3D spheroid model of lung cancer where EndMT does not rely on TGF-β (Kim et al, 2019). In fact, TGF-β signaling appears insufficient in promoting EndMT in GBM but requires the Notch signaling pathway (Marin-Ramos et al, 2019). Such a crosstalk between Notch and TGF-β participates to the formation of a transient mesenchymal/endothelial niche in a murine breast cancer xenograft model (Ghiabi et al, 2015).…”

Section: Regulation Of Endmt Major Inducers In Cancermentioning

confidence: 99%

Endothelial-to-Mesenchymal Transition in Cancer

Clere

Renault

Corre

2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Cancer is one of the most important causes of morbidity and mortality worldwide. Tumor cells grow in a complex microenvironment constituted of immune, stromal, and vascular cells that supports growth, angiogenesis, and metastasis. Endothelial cells (ECs) are major components of the vascular microenvironment. These cells have been described for their plasticity and potential to transdifferentiate into mesenchymal cells through a process known as endothelial-to-mesenchymal transition (EndMT). This complex process is controlled by various factors, by which ECs convert into a phenotype characterized by mesenchymal protein expression and motile, contractile morphology. Initially described in normal heart development, EndMT is now identified in several pathologies, and especially in cancer. In this review, we highlight the process of EndMT in the context of cancer and we discuss it as an important adaptive process of the tumor microenvironment that favors tumor growth and dissemination but also resistance to treatment. Thus, we underline targeting of EndMT as a potential therapeutic strategy.

show abstract

“…It has been shown that POH promotes inhibition of the Ras signaling pathway and, consequently, cell proliferation and apoptosis induction in the phase of promoting dermal carcinogenesis [53]. On the other hand, it has recently been reported that POH can block the transition of the phenotype of undifferentiated mesenchymal cells into endothelial cells (mesenchymal-endothelial transition or TMEnd) derived from human multiform glioblastomas [3]. The authors believe that, as EndTM is essential for the development of tumor angiogenesis phenomena, supporting neoplastic nutrition, this inhibitory effect could, indirectly, inhibit tumor progression and recurrence.…”

Section: Affinity (Kcal/mol) Interaction Interaction Type Frommentioning

confidence: 99%

“…It has been widely used for antineoplastic 2 of 18 treatment [1,2]. The conjugation of POH with temozolomide was shown to block the induction of the pro-angiogenic process, thus demonstrating to be a potential inhibitor of tumor progression and recurrence in glioma stem cells [3]. In therapy against glioblastoma lineage, the efficacy of POH administered intranasally has also been described [4,5].…”

Section: Introductionmentioning

confidence: 99%

Anti-Tumor Efficiency of Perillylalcohol/β-Cyclodextrin Inclusion Complexes in a Sarcoma S180-Induced Mice Model

et al. 2021

View full text Add to dashboard Cite

The low solubility and high volatility of perillyl alcohol (POH) compromise its bioavailability and potential use as chemotherapeutic drug. In this work, we have evaluated the anticancer activity of POH complexed with β-cyclodextrin (β-CD) using three complexation approaches. Molecular docking suggests the hydrogen-bond between POH and β-cyclodextrin in molar proportion was 1:1. Thermal analysis and Fourier-transform infrared spectroscopy (FTIR) confirmed that the POH was enclosed in the β-CD cavity. Also, there was a significant reduction of particle size thereof, indicating a modification of the β-cyclodextrin crystals. The complexes were tested against human L929 fibroblasts after 24 h of incubation showing no signs of cytotoxicity. Concerning the histopathological results, the treatment with POH/β-CD at a dose of 50 mg/kg promoted approximately 60% inhibition of tumor growth in a sarcoma S180-induced mice model and the reduction of nuclear immunoexpression of the Ki67 antigen compared to the control group. Obtained data suggest a significant reduction of cycling cells and tumor proliferation. Our results confirm that complexation of POH/β-CD not only solves the problem related to the volatility of the monoterpene but also increases its efficiency as an antitumor agent.

show abstract

NEO212, a conjugate of temozolomide and perillyl alcohol, blocks the endothelial-to-mesenchymal transition in tumor-associated brain endothelial cells in glioblastoma

Cited by 23 publications

References 51 publications

Endothelial-to-Mesenchymal Transition (EndoMT): Roles in Tumorigenesis, Metastatic Extravasation and Therapy Resistance

Endothelial-to-Mesenchymal Transition (EndoMT): Roles in Tumorigenesis, Metastatic Extravasation and Therapy Resistance

Endothelial-to-Mesenchymal Transition in Cancer

Anti-Tumor Efficiency of Perillylalcohol/β-Cyclodextrin Inclusion Complexes in a Sarcoma S180-Induced Mice Model

Contact Info

Product

Resources

About