Diosmin induces caspase-dependent apoptosis in human glioblastoma cells

SOARES, JULIANA M.; Faria, Bruna Mafra de; Ascari, Lucas M.; Alves-Leon, Soniza Vieira; Souza, Jorge Marcondes de; Soares, Antônio Gomes; Cordeiro, Yraima; Romão, Luciana

doi:10.1590/0001-3765201920191031

Cited by 16 publications

(8 citation statements)

References 59 publications

(36 reference statements)

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“…This result provided another evidence for diosmin’s anti-GBM ability. They found that diosmin provoked caspase-dependent apoptosis in GBM cells, as evidenced by the TUNEL assay [ 39 ]. However, we did not observe significantly increased apoptosis in this study.…”

Section: Discussionmentioning

confidence: 99%

Diosmin Inhibits Glioblastoma Growth through Inhibition of Autophagic Flux

Chang

Chou

et al. 2021

IJMS

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Diosmin, a natural flavone glycoside acquired through dehydrogenation of the analogous flavanone glycoside hesperidin, is plentiful in many citrus fruits. Glioblastoma multiforme (GBM) is the most malignant primary brain tumor; the average survival time of GBM patients is less than 18 months after standard treatment. The present study demonstrated that diosmin, which is able to cross the blood–brain barrier, inhibited GBM cell growth in vitro and in vivo. Diosmin also impeded migration and invasion by GBM8401and LN229 GBM cells by suppressing epithelial-mesenchymal transition, as indicated by increased expression of E-cadherin and decreased expression of Snail and Twist. Diosmin also suppressed autophagic flux, as indicated by increased expression of LC3-II and p62, and induced cell cycle arrest at G1 phase. Importantly, diosmin did not exert serious cytotoxic effects toward control SVG-p12 astrocytes, though it did reduce astrocyte viability at high concentrations. These findings provide potentially helpful support to the development of new therapies for the treatment of GBM.

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Section: Discussionmentioning

confidence: 99%

Diosmin Inhibits Glioblastoma Growth through Inhibition of Autophagic Flux

Chang

Chou

et al. 2021

IJMS

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“…Recent preclinical studies reveal varying levels of GBM selectivity between compounds and cell lines. Tannic acid did not alter the viability of normal rat astrocytes at concentrations up to 75 µM, while diosmin at up to 150 µM remained minimally cytotoxic toward human astrocytes [ 39 , 46 ]. In contrast, withaferin A, cedrol, and rupesin E exhibited dose-dependent cytotoxicity; these compounds inhibited only GBM cells at lower concentrations, but both GBM cells and astrocytes at higher concentrations.…”

Section: Challenges and Considerations In The Use Of Natural Substances For Gbm Treatmentmentioning

confidence: 99%

Natural Compounds in Glioblastoma Therapy: Preclinical Insights, Mechanistic Pathways, and Outlook

Zhai

Siddiqui

Abdellatif

et al. 2021

Cancers

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Glioblastoma (GBM) is an aggressive, often fatal astrocyte-derived tumor of the central nervous system. Conventional medical and surgical interventions have greatly improved survival rates; however, tumor heterogeneity, invasiveness, and chemotherapeutic resistance continue to pose clinical challenges. As such, dietary natural substances—an integral component of the lifestyle medicine approach to chronic diseases—are examined as potential chemotherapeutic agents. These heterogenous substances exert anti-GBM effects by upregulating apoptosis and autophagy, inducing cell cycle arrest, interfering with tumor metabolism, and inhibiting proliferation, neuroinflammation, chemoresistance, angiogenesis, and metastasis. Although these beneficial effects are promising, natural substances’ efficacy in GBM is constrained by their bioavailability and blood–brain barrier permeability; various chemical formulations are proposed to improve their pharmacological properties. Many of the reviewed substances are available as over-the-counter dietary supplements, underscoring their viability as lifestyle interventions. However, clinical trials remain necessary to substantiate the in vitro and in vivo properties of natural substances.

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“…CASP3 encodes caspase 3, which contributes to the final steps in apoptosis, and is also called an executioner caspase 83 . Increased caspase-3 expression in triggers GBM cell death 84 . The inhibition of caspase-3 in brain-resident immune cells promotes GBM progression 85 .…”

Section: Discussionmentioning

confidence: 99%

Identification of potential targets of the curcumin analog CCA-1.1 for glioblastoma treatment : integrated computational analysis and in vitro study

Hermawan

Wulandari

Hanif

et al. 2022

Sci Rep

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The treatment of glioblastoma multiforme (GBM) is challenging owing to its localization in the brain, the limited capacity of brain cells to repair, resistance to conventional therapy, and its aggressiveness. Curcumin has anticancer activity against aggressive cancers, such as leukemia, and GBM; however, its application is limited by its low solubility and bioavailability. Chemoprevention curcumin analog 1.1 (CCA-1.1), a curcumin analog, has better solubility and stability than those of curcumin. In this study, we explored potential targets of CCA-1.1 in GBM (PTCGs) by an integrated computational analysis and in vitro study. Predicted targets of CCA-1.1 obtained using various databases were subjected to comprehensive downstream analyses, including functional annotation, disease and drug association analyses, protein–protein interaction network analyses, analyses of genetic alterations, expression, and associations with survival and immune cell infiltration. Our integrative bioinformatics analysis revealed four candidate targets of CCA-1.1 in GBM: TP53, EGFR, AKT1, and CASP3. In addition to targeting specific proteins with regulatory effects in GBM, CCA-1.1 has the capacity to modulate the immunological milieu. Cytotoxicity of CCA-1.1 was lower than TMZ with an IC50 value of 9.8 μM compared to TMZ with an IC50 of 40 μM. mRNA sequencing revealed EGFR transcript variant 8 was upregulated, whereas EGFRvIII was downregulated in U87 cells after treatment with CCA-1.1. Furthermore, a molecular docking analysis suggested that CCA-1.1 inhibits EGFR with various mutations in GBM, which was confirmed using molecular dynamics simulation, wherein the binding between CCA-1.1 with the mutant EGFR L861Q was stable. For successful clinical translation, the effects of CCA-1.1 need to be confirmed in laboratory studies and clinical trials.

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Diosmin induces caspase-dependent apoptosis in human glioblastoma cells

Cited by 16 publications

References 59 publications

Diosmin Inhibits Glioblastoma Growth through Inhibition of Autophagic Flux

Diosmin Inhibits Glioblastoma Growth through Inhibition of Autophagic Flux

Natural Compounds in Glioblastoma Therapy: Preclinical Insights, Mechanistic Pathways, and Outlook

Identification of potential targets of the curcumin analog CCA-1.1 for glioblastoma treatment : integrated computational analysis and in vitro study

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