Isoorientin induces apoptosis through mitochondrial dysfunction and inhibition of PI3K/Akt signaling pathway in HepG2 cancer cells

Li, Yuan; Wang, Jing; Xiao, Haifang; Xiao, Changlai; Wang, Yutang; Liu, Xuebo

doi:10.1016/j.taap.2012.09.022

Cited by 112 publications

(65 citation statements)

References 55 publications

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“…The activation of HIF‐1 in turn activates the phosphatidylinositol 3‐kinase (PI3K)/Akt cell signaling pathway, which is involved with various cellular behaviors, including tumor malignancy, chemoresistance, and migration . Several previous studies have demonstrated that the activation of PI3K/Akt pathway promotes proliferation and suppresses apoptosis of HepG2 cells . Therefore, the higher level of hypoxia‐induced PI3K/Akt activation of HepG2 cells in MDex‐C hydrogel with higher MDex, as compared to MDex‐DS5 hydrogel, likely played an important role in enhanced viability.…”

Section: Resultsmentioning

confidence: 99%

Comprehensive Examination of Mechanical and Diffusional Effects on Cell Behavior Using a Decoupled 3D Hydrogel System

Kim

Sim

Lee

et al. 2017

Macromolecular Bioscience

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Hydrogels possess several physical and chemical properties suitable for engineering cellular environments for biomedical applications. Despite recent advances in hydrogel systems for cell culture, it is still a significant challenge to independently control the mechanical and diffusional properties of hydrogels, both of which are well known to influence various cell behaviors when using hydrogels as 3D cell culture systems. Controlling the crosslinking density of a hydrogel system to tune the mechanical properties inevitably affects their diffusional properties, as the crosslinking density and diffusion are often inversely correlated. In this study, a polymeric crosslinker is demonstrated that allows for the adjustment of the degree of substitution of reactive functional groups. By using this polymeric crosslinker, the rigidity of the resulting hydrogel is controlled in a wide range without changing the polymer concentration. Furthermore, their diffusional properties, as characterized by their swelling ratios, pore diameters, and drug release rates, are not significantly affected by the changes in the degree of substitution. 3D cell studies using this hydrogel system successfully demonstrate the varying effects of mechanical properties on different cell types, whereas those in a conventional hydrogel system are more significantly influenced by changes in diffusional properties.

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Section: Resultsmentioning

confidence: 99%

Comprehensive Examination of Mechanical and Diffusional Effects on Cell Behavior Using a Decoupled 3D Hydrogel System

Kim

Sim

Lee

et al. 2017

Macromolecular Bioscience

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“…To evaluated the participation of ROS production and iNOS induction in the mechanism of OGD‐induced cell damage, we have used NAC (5 mM; Yuan et al . ) a ROS scavenger, and 1400W (20 or 50 μM; Cárdenas et al . ) a selective iNOS inhibitor, to assess the hippocampal cellular viability after OGD.…”

Section: Resultsmentioning

confidence: 99%

Guanosine controls inflammatory pathways to afford neuroprotection of hippocampal slices under oxygen and glucose deprivation conditions

Dal-Cim

Ludka

Martins

et al. 2013

Journal of Neurochemistry

124

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Guanosine (GUO) is an endogenous modulator of glutamatergic excitotoxicity and has been shown to promote neuroprotection in in vivo and in vitro models of neurotoxicity. This study was designed to understand the neuroprotective mechanism of GUO against oxidative damage promoted by oxygen/ glucose deprivation and reoxygenation (OGD). GUO (100 lM) reduced reactive oxygen species production and prevented mitochondrial membrane depolarization induced by OGD. GUO also exhibited anti-inflammatory actions as inhibition of nuclear factor kappa B activation and reduction of inducible nitric oxide synthase induction induced by OGD. These GUO neuroprotective effects were mediated by adenosine A 1 receptor, phosphatidylinositol-3 kinase and MAPK/ERK. Furthermore, GUO recovered the impairment of glutamate uptake caused by OGD, an effect that occurred via a Pertussis toxin-sensitive G-protein-coupled signaling, blockade of adenosine A 2A receptors (A 2A R), but not via A 1 receptor. The modulation of glutamate uptake by GUO also involved MAPK/ ERK activation. In conclusion, GUO, by modulating adenosine receptor function and activating MAPK/ERK, affords neuroprotection of hippocampal slices subjected to OGD by a mechanism that implicates the following: (i) prevention of mitochondrial membrane depolarization, (ii) reduction of oxidative stress, (iii) regulation of inflammation by inhibition of nuclear factor kappa B and inducible nitric oxide synthase, and (iv) promoting glutamate uptake.

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“…[4987] Cancer cells exhibit a higher and more persistent oxidative stress level compared to normal cells, rendering malignant cells more vulnerable to being killed by drugs that boost increased ROS levels, such as some flavonoids. [88899091] Whether a flavonoid acts as anti- or prooxidant depends on its dose, cell type, and also culture conditions. [379092]…”

Section: Flavonoids As Potent Anticancer Agentsmentioning

confidence: 99%

Cytotoxicity of dietary flavonoids on different human cancer types

Sak¹

2014

Phcog Rev

403

239

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Flavonoids are ubiquitous in nature. They are also in food, providing an essential link between diet and prevention of chronic diseases including cancer. Anticancer effects of these polyphenols depend on several factors: Their chemical structure and concentration, and also on the type of cancer. Malignant cells from different tissues reveal somewhat different sensitivity toward flavonoids and, therefore, the preferences of the most common dietary flavonoids to various human cancer types are analyzed in this review. While luteolin and kaempferol can be considered as promising candidate agents for treatment of gastric and ovarian cancers, respectively, apigenin, chrysin, and luteolin have good perspectives as potent antitumor agents for cervical cancer; cells from main sites of flavonoid metabolism (colon and liver) reveal rather large fluctuations in anticancer activity probably due to exposure to various metabolites with different activities. Anticancer effect of flavonoids toward blood cancer cells depend on their myeloid, lymphoid, or erythroid origin; cytotoxic effects of flavonoids on breast and prostate cancer cells are highly related to the expression of hormone receptors. Different flavonoids are often preferentially present in certain food items, and knowledge about the malignant tissue-specific anticancer effects of flavonoids could be purposely applied both in chemoprevention as well as in cancer treatment.

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Isoorientin induces apoptosis through mitochondrial dysfunction and inhibition of PI3K/Akt signaling pathway in HepG2 cancer cells

Cited by 112 publications

References 55 publications

Comprehensive Examination of Mechanical and Diffusional Effects on Cell Behavior Using a Decoupled 3D Hydrogel System

Comprehensive Examination of Mechanical and Diffusional Effects on Cell Behavior Using a Decoupled 3D Hydrogel System

Guanosine controls inflammatory pathways to afford neuroprotection of hippocampal slices under oxygen and glucose deprivation conditions

Cytotoxicity of dietary flavonoids on different human cancer types

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