Isorhamnetin Inhibits Reactive Oxygen Species-Dependent Hypoxia Inducible Factor (HIF)-1α Accumulation

Seo, Suho; Seo, Kyuhwa; Ki, Sung Hwan; Shin, Sook

doi:10.1248/bpb.b16-00414

Cited by 38 publications

(23 citation statements)

References 30 publications

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“…The beneficial effects of isorhamnetin, such as anti-inflammatory, antioxidant and anti-cancer have been reported in various tissues [ 36 , 37 , 38 ]. Seo et al [ 39 ] determined that the antioxidant activity of isorhamnetin was correlated with its anti-cancer effects on colorectal cancer cells. The results demonstrated that isorhamnetin inhibits reactive oxygen species (ROS)-mediated hypoxia-induced hypoxia inducible factor-1α (HIF-1α) accumulation, which contributes to its anti-metastatic efficacy.…”

Section: Resultsmentioning

confidence: 99%

LC-ESI-MS/MS Identification of Biologically Active Phenolic Compounds in Mistletoe Berry Extracts from Different Host Trees

et al. 2017

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A new, rapid, sensitive and selective liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method was developed to determine the content of flavonoid aglycones and phenolic acids in mistletoe berries (Viscum album L.) harvested from six different Polish host trees. Additionally, the total phenolic content (TPC) and total flavonoid content (TFC) as well as an antioxidant and antiproliferative activity were evaluated for the first time. The plant material was selectively extracted using ultrasound assisted maceration with methanol/water (8:2) solution. The obtained TPC and TFC results varied from 7.146 to 9.345 mg GA g−1 and from 1.888 to 2.888 mg Q g−1 of dry extracts, respectively. The LC-ESI-MS/MS analysis demonstrated the highest content of phenolic acids in mistletoe berries from Populus nigra ‘Italica’ L. and flavonoid aglycones in mistletoe berries from Tilia cordata Mill. (354.45 µg and 5.955 µg per g dry extract, respectively). The moderate antioxidant activity of investigated extracts was obtained. The studies revealed that the examined extracts decreased the proliferation of human colon adenocarcinoma cells line LS180 in a dose-dependent manner without cytotoxicity in the human colon epithelial cell line CCD 841 CoTr. Moreover, the obtained results suggest considerable impact of polyphenols on the anticancer activity of these extracts.

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Section: Resultsmentioning

confidence: 99%

LC-ESI-MS/MS Identification of Biologically Active Phenolic Compounds in Mistletoe Berry Extracts from Different Host Trees

et al. 2017

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“…This compound is one of the metabolites of quercetin that is structurally similar to kaempferol, also known as 3'-O-methyl quercetin (Castrillo et al 1986;Rösch et al 2004;Chen et al 2013). Isorhamnetin exhibits many biological properties due to its anti-inflammatory, antioxidant and metabolic properties (Luo et al 2015;Seo et al 2016;Yang et al 2016;Abdallah and Esmat 2017;Qi et al 2018), and is also considered to have the potential of anti-cancer agents in the results of various cancer cell models. According to previous studies, isorhamnetin has been reported to prevent the proliferation of human leukemia, breast cancer, colon cancer and cervical cancer cells through G2/M phase arrest (Li et al 2014;Wu et al 2016;Wei et al 2018;Zhang et al 2018), and to induce mitotic block in non-small cell lung carcinoma cells, thus enhancing cisplatin-and carboplatin-induced G2/M arrest (Zhang et al 2015).…”

Section: Introductionmentioning

confidence: 99%

Isorhamnetin induces ROS-dependent cycle arrest at G2/M phase and apoptosis in human hepatocarcinoma Hep3B cells

Choi

2019

gpb

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Isorhamnetin is a 3'-O-methylated metabolite of quercetin that is found predominantly in a variety of medicinal plants. Although many previous studies have reported that this flavonol has diverse health-promoting effects, evidence for the underlying molecular mechanism of anti-cancer efficacy is still lacking. In this study, it was examined the anti-proliferative effect of isorhamnetin on human hepatocarcinoma Hep3B cells, and found that isorhamnetin induced cell cycle arrest at G2/M phase and apoptosis. Isorhamnetin-induced G2/M arrest was associated with decreased expression of proliferating cell nuclear antigen as well as cyclin A and cyclin B1. However, isorhamnetin increased expression of p21WAF1/CIP1, a cyclin-dependent kinase (Cdk) inhibitor, and increased p21 complexed with Cdk2 and Cdc2. In addition, isorhamnetin-induced apoptosis was associated with increased expression of Fas/Fas ligand, reduced ratio of Bcl-2/Bax expression, truncation of Bid, cytosolic release of cytochrome c, and activation of caspase-8,-9 and-3. Isorhamnetin also enhanced intracellular levels of reactive oxygen species (ROS), while the addition of N-acetyl cysteine (NAC), a ROS inhibitor, significantly diminished isorhamnetin-induced mitochondrial dysfunction. Furthermore, the interruption of ROS generation using NAC significantly attenuated isorhamnetinmediated G2/M arrest and apoptosis. Collectively, this is the first report to show that isorhamnetin inhibited the proliferation of human hepatocarcinoma cells by ROS-dependent arrest of the cell cycle at the G2/M phase and induction of apoptosis.

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“…18 Therefore, we used the CoCl 2 to create a hypoxic culture condition and revealed the ability of inhibition of HIF-1α 18 Therefore, we used the CoCl 2 to create a hypoxic culture condition and revealed the ability of inhibition of HIF-1α…”

Section: Inhibition Of Hif-1α and Vegf Expression By Mir-148a In Thmentioning

confidence: 99%

“…From the previous study demonstrated by Seo et al, CoCl 2 is a hypoxia mimetic agent. 18 Therefore, we used the CoCl 2 to create a hypoxic culture condition and revealed the ability of inhibition of HIF-1α and VEGF expression by miR-148a under the hypoxic culture medium. and Friday.…”

Section: Inhibition Of Hif-1α and Vegf Expression By Mir-148a In Thmentioning

confidence: 99%

miR‐148a inhibits early relapsed colorectal cancers and the secretion of VEGF by indirectly targeting HIF‐1α under non‐hypoxia/hypoxia conditions

Tsai

Zhang

Chen

et al. 2019

J Cellular Molecular Medi

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Vascular endothelial growth factor (VEGF) is correlated with angiogenesis and early relapse of colorectal cancer (CRC). This study investigated the role of miR‐148a in the regulation of VEGF/angiogenesis and early relapse of CRC. We established a stable clone with miR‐148a expression in HCT116 and HT29 cell lines and created a hypoxic condition by using CoCl 2 to determine the underlying mechanism of miR‐148a . The effects of miR‐148a on the phosphoryl‐ERK (pERK)/hypoxia‐inducible factor‐1α (HIF‐1α)/VEGF pathway were evaluated through Western blotting and the inhibitory effect of miR‐148a on angiogenesis was demonstrated through a tube formation assay. Sixty‐three CRC tissues (28 early relapse and 35 non‐early relapse) were analysed to assess the relationship between miR‐148a and HIF‐1α/VEGF. The protein expression of pERK/HIF‐1α/VEGF in HCT116 and HT29 cells was significantly decreased by miR‐148a (all P < 0.05). The protein expression of VEGF/HIF‐1α was strongly inversely associated with the expression of miR‐148a in the 63 CRC tissue samples (all P < 0.05). Tube formation assay demonstrated that miR‐148a significantly obliterated angiogenesis. miR‐148a suppresses VEGF through down‐regulation of the pERK/HIF‐1α/VEGF pathway and might lead to the inhibition of angiogenesis; miR‐148a down‐regulation increased the early relapse rate of CRC. This demonstrates that miR‐148a is a potential diagnostic and therapeutic target.

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Isorhamnetin Inhibits Reactive Oxygen Species-Dependent Hypoxia Inducible Factor (HIF)-1α Accumulation

Cited by 38 publications

References 30 publications

LC-ESI-MS/MS Identification of Biologically Active Phenolic Compounds in Mistletoe Berry Extracts from Different Host Trees

LC-ESI-MS/MS Identification of Biologically Active Phenolic Compounds in Mistletoe Berry Extracts from Different Host Trees

Isorhamnetin induces ROS-dependent cycle arrest at G2/M phase and apoptosis in human hepatocarcinoma Hep3B cells

miR‐148a inhibits early relapsed colorectal cancers and the secretion of VEGF by indirectly targeting HIF‐1α under non‐hypoxia/hypoxia conditions

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