Hesperetin-etoposide combinations induce cytotoxicity in U2OS cells: Implications on therapeutic developments for osteosarcoma

Coutinho, Laura; Oliveira, Helena; Pacheco, Ana Rita; Almeida, Luís; Pimentel, Francisco; Santos, Conceição; Oliveira, José Miguel P. Ferreira de

doi:10.1016/j.dnarep.2016.12.006

Cited by 19 publications

(10 citation statements)

References 29 publications

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“…Our research group has demonstrated that increasing concentrations of hesperetin significantly inhibited the proliferation of cancer cells in vitro and in vivo ( Zhang et al, 2015 ; Wu et al, 2016 ). More importantly, hesperetin is not only a potential anti-cancer drug, but also serves as a chemical sensitizer ( Coutinho et al, 2017 ; Lee et al, 2019 ; Wang et al, 2019 ). Wang et al reported that hesperetin was likely to act as an accelerator for the anti-cancer effect of DDP in lung adenocarcinoma ( Wang et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Hesperetin Promotes Cisplatin−Induced Apoptosis of Gastric Cancer In Vitro and In Vivo by Upregulating PTEN Expression

Liu

et al. 2020

Front. Pharmacol.

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As one of the most common malignant gastrointestinal tumors, gastric cancer (GC) has a high incidence and poor prognosis. Cisplatin (DDP) is often used as chemotherapy for advanced GC; however, the high incidence of drug resistance remains a problem. The use of several anti-tumor drugs as combined chemotherapy is an effective strategy. Hesperetin has anti-tumor ability via its pro-apoptotic effect on various human cancers, both in vitro and in vivo , with no significant toxicity. However, a combination of DDP and hesperetin in GC has not been reported. The present study aimed to investigate the in vitro and in vivo chemosensitization effect and mechanism of hesperetin-augmented DDP-induced apoptosis of GC. The proliferation of GC ty -60cells was inhibited significantly in a time and dose-dependent manner by combined treatment of DDP with hesperetin. Hesperetin markedly increased DDP-induced apoptosis of GC cell lines. In a xenograft tumor mouse model, markedly better tumor suppression was observed after treatment with DDP plus hesperetin compared with that of either agent alone. Additionally, the combination of DDP and hesperetin remarkably increased the expression levels of phosphatase and tensin homolog (PTEN) and Cytochrome C (Cyt C), and significantly decreased the levels of phosphorylated protein kinase B (p-AKT) and CyclinD1. DDP and hesperetin also induced significant increases in apoptosis inducing factor (AIF), BCL2 associated X, apoptosis regulator (BAX), cleaved caspase-9, and cleaved caspase-3, and decreased B-cell lymphoma 2 (BCL2), caspase-9, and caspase-3 levels. Thus, we demonstrated that hesperetin could inhibit the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT signaling pathway and induce the mitochondrial pathway via upregulating PTEN expression, thereby significantly enhancing DDP’s anti-tumor effect on GC. Hesperetin is a potential chemotherapeutic agent for GC and merits further clinical investigation.

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Section: Discussionmentioning

confidence: 99%

Hesperetin Promotes Cisplatin−Induced Apoptosis of Gastric Cancer In Vitro and In Vivo by Upregulating PTEN Expression

Liu

et al. 2020

Front. Pharmacol.

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“…The higher cytotoxic action of hesperidin nanoparticles could be due to slow cellular uptake and intracellular distribution of hesperidin nanoparticles because of its slow release behavior. Flavanones such as hesperidin and hesperitin relying on the cancer cell line and exposure conditions can stimulate apoptosis, DNA damage, diminish the invasive potential and reduce NF-jB activity [45]. A study on the mechanism by which hesperidin nanoparticles induces cell death is needed and will be extended for further investigations.…”

Section: Colony Forming Activity and Cytotoxicity Assaymentioning

confidence: 99%

Fabrication of hesperidin nanoparticles loaded by poly lactic co-Glycolic acid for improved therapeutic efficiency and cytotoxicity

Ali

Sulaiman

Al-Halbosiy

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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Hesperidin, as a flavonone, is recognized as promising anti-inflammatory, antioxidant, and anticancer agent. Its poor bioavailability is crucial bottleneck for therapeutic efficacy. To enhance the stability and bioactive potentials, hesperidin-PLGA-Poloxamer 407 was successfully prepared to minimize or overcome problems associated with hesperidin absorption. The characteristics of nanohesperidin were testing by in vitro dissolution study, XRD, FTIR, PSA and SEM. Antioxidant effects of nanohesperidin were studied. The structure-activity relationship analysis with antioxidant pharmacophore has been performed by using density functional theory method and quantum chemical calculations. The structural properties were investigated using Becke three-parameter hybrid exchange and the Lee-Yang-Parr correction functional methods. Nanohesperidin was found to decrease the H 2 O 2 activity-induced DNA instability. Blood compatibility on human erythrocytes was confirmed by haemolytic and in vitro toxicity assessments. The in vitro anticancer activity of nanohesperidin towards MCF-7 cells using various parameters was carried out. The nanohesperidin was found to exert cell growth arrest, activated DNA fragmentation and induced apoptotic cell death through caspase-3 and p53-dependent pathways. These findings showed that nanohesperidin play an important role in its anticancer effects, suggesting might be used for clinical trials and can represent driving formulation for novel chemotherapeutic agents.

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“…a major decrease in HDAC activity was discovered once treatment with sulforaphane alone or together with the antineoplastic drug methotrexate sodium ( Figure 2). In agreement with this knowledge Ho et al incontestible that sulforaphane inhibits HDAC activity in the human large intestine and glandular carcinoma cells by enhancing simple protein acylation, derepression of P21 and Bax, and induction of cell cycle arrest/apoptosis that result in cancer interference [35] [36].…”

Section: Ferreira First State Oliveira Et Al (2014) Additionallymentioning

confidence: 67%

“…reportable that the MG-63 osteogenic sarcoma cell line was exposed to SFN at a dietary concentration (5 μM) caused in genomic instability by the associate enlarged range of polymer breaks [34] [35].…”

Section: Ferreira First State Oliveira Et Al (2014) Additionallymentioning

confidence: 98%

Role of Sulforaphane on Histone Deacetylase Activity in Solid Ehrlich Carcinoma

El-Keey¹,

Ibrahim²,

El-Ghonamy³

et al. 2020

JBM

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Histone acylation is one in every of the posttranslational modification that incorporates a role within the regulation of sequence expression. This study was aimed to ameliorate neoplasm cell model Solid Ehrlich malignant neoplastic disease with sulforaphane extracted from cabbage alone and together with immune suppressant drug (MTX) by study the activity of simple protein deacetylase accelerator (HDAC). In this study, sulforaphane was extracted from cabbage leaves and evaluated victimization GC-MS and ultraviolet illumination spectrophotometry. 60 white male rats were divided into six equal groups. Group I: management ordinarily. The remaining mice were subjected to Ehrlich neoplasm cells. Group II: Tumor-bearing group. Group III: immune suppressant drug "MTX" treated group. Group IV, V treated with SFN before and when Paul Ehrlich cells implantation group VI (Methotrexate and sulforaphane-treated group). This result showed that sulforaphane was extracted from cabbage (Brassica oleracea) in concentration of 833 µg/g leave. HDAC was attenuated when treatment with sulforaphane after treatment with methotrexate or sulforaphane alone. The desoxyribonucleic acid injury was attenuated in neoplasm tissue of tumor-bearing mice when treatment with immune suppressant drug and hyperbolic considerably in tumor tissue of tumor-bearing mice treated with sulforaphane before and after carcinogenesis and together with methotrexate treatment after carcinogenesis.

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Hesperetin-etoposide combinations induce cytotoxicity in U2OS cells: Implications on therapeutic developments for osteosarcoma

Cited by 19 publications

References 29 publications

Hesperetin Promotes Cisplatin−Induced Apoptosis of Gastric Cancer In Vitro and In Vivo by Upregulating PTEN Expression

Hesperetin Promotes Cisplatin−Induced Apoptosis of Gastric Cancer In Vitro and In Vivo by Upregulating PTEN Expression

Fabrication of hesperidin nanoparticles loaded by poly lactic co-Glycolic acid for improved therapeutic efficiency and cytotoxicity

Role of Sulforaphane on Histone Deacetylase Activity in Solid Ehrlich Carcinoma

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