Cyclopamine sensitizes glioblastoma cells to temozolomide treatment through Sonic hedgehog pathway

Carballo, Gabriela Basile; Matias, Diana; Ribeiro, Jéssica Honorato; Pessôa, Luciana Fontes; Arrais-Neto, Ananias Matos; Spohr, Tânia Cristina Leite de Sampaio e

doi:10.1016/j.lfs.2020.118027

Cited by 13 publications

(8 citation statements)

References 58 publications

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“…Moreover, GANT61, a GLI inhibitor, potentiates the cytotoxic effect of temozolomide, which is a first-line chemotherapy treatment for glioma, thus becoming a promising in vitro strategy for glioma treatment [48,49]. The inhibitor of the Hh pathway, cyclopamine, could potentiate the temozolomide effect in cancer stemlike cells and glioma cell lines in vitro [50]. Studies showed that arsenic trioxide (ATO)-mediated Hh/ Notch inhibition could be used in the clinic as it represents a promising targeted therapy approach for the elimination of glioma stem-like cells [51].…”

Section: Discussionmentioning

confidence: 99%

GLI1 is involved in HIF-1α-induced migration, invasion, and epithelial-mesenchymal transition in glioma cells

Lin¹,

Guo²

2022

Folia Histochem Cytobiol.

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This article is available in open access under Creative Common Attribution-Non-Commercial-No Derivatives 4.0 International (CC BY-NC-ND 4.0) license, allowing to download articles and share them with others as long as they credit the authors and the publisher, but without permission to change them in any way or use them commercially. www.journals.viamedica.pl/folia_histochemica_cytobiologica ©Polish Society for Histochemistry and Cytochemistry Folia Histochem Cytobiol.

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Section: Discussionmentioning

confidence: 99%

GLI1 is involved in HIF-1α-induced migration, invasion, and epithelial-mesenchymal transition in glioma cells

Lin¹,

Guo²

2022

Folia Histochem Cytobiol.

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“…These effects were reflected in the functional experiments where we reported a significant increase of nuclear Ki-67 MFI and migration index in purmorphamine treated cells reverted by cyclopamine treatment. Previously studies demonstrated that cyclopamine interferes with GBM cell viability and stemness showing a synergistic effect with temozolomide [ 45 , 65 ]. However, in these studies, higher concentrations and long-time exposures of cyclopamine were used, whereas in our study we evaluated acute effects of both SMO stimulation and CX43 inhibition in order to find whether these treatments prelude to increasing migration and proliferation of GBM cell lines and may be reverted by cotreatments.…”

Section: Discussionmentioning

confidence: 99%

Connexin 43 and Sonic Hedgehog Pathway Interplay in Glioblastoma Cell Proliferation and Migration

Torrisi

Alberghina

Furno

et al. 2021

Biology

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Glioblastoma (GBM) represents the most common primary brain tumor within the adult population. Current therapeutic options are still limited by high rate of recurrences and signalling axes that promote GBM aggressiveness. The contribution of gap junctions (GJs) to tumor growth and progression has been proven by experimental evidence. Concomitantly, tumor microenvironment has received increasing interest as a critical process in dysregulation and homeostatic escape, finding a close link between molecular mechanisms involved in connexin 43 (CX43)-based intercellular communication and tumorigenesis. Moreover, evidence has come to suggest a crucial role of sonic hedgehog (SHH) signalling pathway in GBM proliferation, cell fate and differentiation. Herein, we used two human GBM cell lines, modulating SHH signalling and CX43-based intercellular communication in in vitro models using proliferation and migration assays. Our evidence suggests that modulation of the SHH effector smoothened (SMO), by using a known agonist (i.e., purmorphamine) and a known antagonist (i.e., cyclopamine), affects the CX43 expression levels and therefore the related functions. Moreover, SMO activation also increased cell proliferation and migration. Importantly, inhibition of CX43 channels was able to prevent SMO-induced effects. SHH pathway and CX43 interplay acts inducing tumorigenic program and supporting cell migration, likely representing druggable targets to develop new therapeutic strategies for GBM.

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“…SHH signaling is also important in the migration of GSCs into normal brain tissues . Inhibition of the SHH pathway sensitizes GSCs to TMZ treatment, implying the role of the SHH pathway in controlling chemoresistance . Therefore, pharmacologic inhibitors can improve the efficacy of conventional therapies by targeting this pathway and inhibiting GSC growth.…”

Section: Glioma Stem Cellsmentioning

confidence: 99%

Nanomedicines Targeting Glioma Stem Cells

Sabu

Liu

et al. 2022

ACS Appl. Mater. Interfaces

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Glioblastoma (GBM), classified as a grade IV glioma, is a rapidly growing, aggressive, and most commonly occurring tumor of the central nervous system. Despite the therapeutic advances, it carries an ominous prognosis, with a median survival of 14.6 months after diagnosis. Accumulating evidence suggests that cancer stem cells in GBM, termed glioma stem cells (GSCs), play a crucial role in tumor propagation, treatment resistance, and tumor recurrence. GSCs, possessing the capacity for self-renewal and multilineage differentiation, are responsible for tumor growth and heterogeneity, leading to primary obstacles to current cancer therapy. In this respect, increasing efforts have been devoted to the development of anti-GSC strategies based on targeting GSC surface markers, blockage of essential signaling pathways of GSCs, and manipulating the tumor microenvironment (GSC niches). In this review, we will discuss the research knowledge regarding GSC-based therapy and the underlying mechanisms for the treatment of GBM. Given the rapid progression in nanotechnology, innovative nanomedicines developed for GSC targeting will also be highlighted from the perspective of rationale, advantages, and limitations. The goal of this review is to provide broader understanding and key considerations toward the future direction of GSC-based nanotheranostics to fight against GBM.

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Cyclopamine sensitizes glioblastoma cells to temozolomide treatment through Sonic hedgehog pathway

Cited by 13 publications

References 58 publications

GLI1 is involved in HIF-1α-induced migration, invasion, and epithelial-mesenchymal transition in glioma cells

GLI1 is involved in HIF-1α-induced migration, invasion, and epithelial-mesenchymal transition in glioma cells

Connexin 43 and Sonic Hedgehog Pathway Interplay in Glioblastoma Cell Proliferation and Migration

Nanomedicines Targeting Glioma Stem Cells

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