Sulforaphane-cysteine inhibited migration and invasion via enhancing mitophagosome fusion to lysosome in human glioblastoma cells

Zhou, Yan; Wang, Yalin; Wu, Shuqi; Yan, Yu-Ting; Hu, Yongbin; Zheng, Zhongnan; Li, Juntao; Wu, Wei

doi:10.1038/s41419-020-03024-5

Cited by 18 publications

(13 citation statements)

References 48 publications

(74 reference statements)

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“…Adhesion molecules, membrane proteins, or invasion-linked proteins may play roles in tumor invasion and migration. In human glioblastoma cells, sulforaphane-cysteine suppressed the invasion and migration by increasing the fusion of mitophagosome to the lysosome (Zhou et al, 2020). Collectively, these findings might help in developing low-toxicity and high-efficiency anticancer drugs to suppress invasion and migration in GBM.…”

Section: Natural Molecules and Blood-brain Barrier Permeabilitymentioning

confidence: 83%

Natural Small Molecules Targeting NF-κB Signaling in Glioblastoma

et al. 2021

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Nuclear factor-κB (NF-κB) is a transcription factor that regulates various genes that mediate various cellular activities, including propagation, differentiation, motility, and survival. Abnormal activation of NF-κB is a common incidence in several cancers. Glioblastoma multiforme (GBM) is the most aggressive brain cancer described by high cellular heterogeneity and almost unavoidable relapse following surgery and resistance to traditional therapy. In GBM, NF-κB is abnormally activated by various stimuli. Its function has been associated with different processes, including regulation of cancer cells with stem-like phenotypes, invasion of cancer cells, and radiotherapy resistance identification of mesenchymal cells. Even though multimodal therapeutic approaches such as surgery, radiation therapy, and chemotherapeutic drugs are used for treating GBM, however; the estimated mortality rate for GBM patients is around 1 year. Therefore, it is necessary to find out new therapeutic approaches for treating GBM. Many studies are focusing on therapeutics having less adverse effects owing to the failure of conventional chemotherapy and targeted agents. Several studies of compounds suggested the involvement of NF-κB signaling pathways in the growth and development of a tumor and GBM cell apoptosis. In this review, we highlight the involvement of NF-κB signaling in the molecular understanding of GBM and natural compounds targeting NF-κB signaling.

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Section: Natural Molecules and Blood-brain Barrier Permeabilitymentioning

confidence: 83%

Natural Small Molecules Targeting NF-κB Signaling in Glioblastoma

et al. 2021

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“…This makes microtubule polymerization inhibitors as well as stabilizing and/or destabilizing agents a good target for the anticancer therapy (Calinescu et al 2016). Zhou et al (2020) found that sulforaphanecysteine disrupted microtubules by ERK1/2 phosphorylation-mediated downregulation of α-tubulin and Stathmin-1 leading to the inhibition of U87-MG and U373-MG cells migration and invasion. The authors noticed also lower expressions of α-tubulin-mediated mitophagy-associated proteins (Zhou et al 2020).…”

Section: Discussionmentioning

confidence: 95%

“…Zhou et al (2020) found that sulforaphanecysteine disrupted microtubules by ERK1/2 phosphorylation-mediated downregulation of α-tubulin and Stathmin-1 leading to the inhibition of U87-MG and U373-MG cells migration and invasion. The authors noticed also lower expressions of α-tubulin-mediated mitophagy-associated proteins (Zhou et al 2020). This con rms our results since we observed a decrease in the alpha-tubulin level after perphenazine (1.0 µM) and prochlorperazine (0.5 and 1.0 µM) treatment of U87-MG cells accompanied by a decline in the U87-MG migration and invasion.…”

Section: Discussionmentioning

confidence: 95%

Perphenazine and Prochlorperazine Decrease Glioblastoma U87-MG Cells Migration and Invasion: Analysis of the ABCB1 and ABCG2 Transporters, E-Cadherin, α-Tubulin, and Integrins (α3, α5, and β1) Levels.

Otręba

Stojko

Kabała‐Dzik

et al. 2021

Preprint

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Purpose: Glioblastoma multiforme is the most frequent malignant brain tumor as well as one of the most lethal and untreatable human tumors with a very poor survival rate. Thus, novel and effective strategies of treatment are required. Integrins play a crucial role in the regulation of cellular adhesion and invasion. Moreover, integrins and alpha-tubulin are very important in cell migration, while E-cadherin plays the main role in tumor metastasis. Their ability to penetrate the BBB and signs of intracerebral activity are very important in glioblastoma therapy. ABC transporters ABCB1 and ABCG2, which are localized in the brain endothelial capillaries of BBB, play a crucial role in the development of multidrug resistance, and are modulated by phenothiazine derivatives. Methods: The impact on the motility of human glioblastoma U87-MG was evaluated with a wound healing assay; cellular migration, and invasion by the transwell assay, while ABCB1, ABCG2, E-cadherin, α-tubulin, and integrins content was determined with the Western blot.Results: This study explores the effect of perphenazine and prochlorperazine on ABCB1, ABCG2, E-cadherin, α-tubulin, and integrins (α3, α5, and β1) amount as well as on migration and invasion ability of human glioblastoma (U87-MG) cells. The results suggest that perphenazine and prochlorperazine modulate multidrug resistance proteins (they decrease ABCB1 and increase ABCG2), E-cadherin, α-tubulin, and integrins amount as well as impair migration and invasion of the U87-MG cell line. Conclusions: The decrease of migration and invasion ability after phenothiazine derivatives treatment due to the increase of ABCG2 and E-cadherin as well as the decrease of α-tubulin, and integrins amounts can support the hypothesis that perphenazine and prochlorperazine have the anticancer effect on human glioblastoma U87-MG cells.

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“…Initially, in yeast, cells only used the autophagy program to fulfill autologous metabolic needs or renew certain organelles, thereby maintaining the vitality of cells suffering from nutritional deterioration [ 53 ]. However, in higher eukaryotes, autophagy plays much more complicated and multifunctional roles in regulating cell survival and death, especially in cancer cells [ 27 , 29 , 54 , 55 ]. The commonly studied proteins closely related to the autophagy program mainly include LC3B and p62 [ 55 – 57 ], and their expression represents the differential autophagy status and output.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological inhibition of Ref-1 enhances the therapeutic sensitivity of papillary thyroid carcinoma to vemurafenib

Zhang

Tian

et al. 2022

Cell Death Dis

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The use of the BRAF inhibitor vemurafenib exhibits drug resistance in the treatment of thyroid cancer (TC), and finding more effective multitarget combination therapies may be an important solution. In the present study, we found strong correlations between Ref-1 high expression and BRAF mutation, lymph node metastasis, and TNM stage. The oxidative stress environment induced by structural activation of BRAF upregulates the expression of Ref-1, which caused intrinsic resistance of PTC to vemurafenib. Combination inhibition of the Ref-1 redox function and BRAF could enhance the antitumor effects of vemurafenib, which was achieved by blocking the action of Ref-1 on BRAF proteins. Furthermore, combination treatment could cause an overload of autophagic flux via excessive AMPK protein activation, causing cell senescence and cell death in vitro. And combined administration of Ref-1 and vemurafenib in vivo suppressed PTC cell growth and metastasis in a cell-based lung metastatic tumor model and xenogeneic subcutaneous tumor model. Collectively, our study provides evidence that Ref-1 upregulation via constitutive activation of BRAF in PTC contributes to intrinsic resistance to vemurafenib. Combined treatment with a Ref-1 redox inhibitor and a BRAF inhibitor could make PTC more sensitive to vemurafenib and enhance the antitumor effects of vemurafenib by further inhibiting the MAPK pathway and activating the excessive autophagy and related senescence process.

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Sulforaphane-cysteine inhibited migration and invasion via enhancing mitophagosome fusion to lysosome in human glioblastoma cells

Cited by 18 publications

References 48 publications

Natural Small Molecules Targeting NF-κB Signaling in Glioblastoma

Natural Small Molecules Targeting NF-κB Signaling in Glioblastoma

Perphenazine and Prochlorperazine Decrease Glioblastoma U87-MG Cells Migration and Invasion: Analysis of the ABCB1 and ABCG2 Transporters, E-Cadherin, α-Tubulin, and Integrins (α3, α5, and β1) Levels.

Pharmacological inhibition of Ref-1 enhances the therapeutic sensitivity of papillary thyroid carcinoma to vemurafenib

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