Wogonin inhibits the proliferation of myelodysplastic syndrome cells through the induction of cell cycle arrest and apoptosis

Lu, Huixia; Gao, Feng; Shu, Guofang; Xia, Guohua; Shao, Zongshu; Lu, Hangqin; Cheng, Kun

doi:10.3892/mmr.2015.4353

Cited by 10 publications

(10 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Western blot analysis was performed as described previously ( 7 ). Briefly, aliquots of cell lysates containing 25 µg protein were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis.…”

Section: Methodsmentioning

confidence: 99%

Modulation of G2/M cell cycle arrest and apoptosis by luteolin in human colon cancer cells and xenografts

et al. 2017

Self Cite

View full text Add to dashboard Cite

The aim of the present study was to investigate the underlying molecular mechanisms of the potent cell cycle inhibition and apoptotic effect of luteolin on LoVo human colon cancer cells. In the present study, Cell Counting kit-8 assay revealed that luteolin exerted notable cytotoxicity on LoVo cells in a dose- and time-dependent manner, with a 50% inhibitory concentration value of 66.70 and 30.47 µmol/l at the time points of 24 and 72 h, respectively. Flow cytometric analysis confirmed that luteolin promoted cell cycle arrest at the G2/M phase, and subsequently induced cell apoptosis. Western blot analysis further revealed that luteolin exhibited an inhibitory effect on the proliferation of LoVo cells by inhibiting cell cycle arrest at the G2/M phase transition, with an inactivation of cyclin B1/cell division cycle 2 and induction of cell apoptosis, in part via cytochrome c- and deoxyadenosine triphosphate-mediated activation of apoptotic protease activating factor 1. In vivo studies revealed that luteolin effectively decreased the colon tumor body weight of mice. Therefore, the evidence suggests that luteolin may be a potential chemopreventive and chemotherapeutic agent against human colon cancer.

show abstract

Section: Methodsmentioning

confidence: 99%

Modulation of G2/M cell cycle arrest and apoptosis by luteolin in human colon cancer cells and xenografts

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…5,7-dihydroxy-8-methoxyflavone, or wogonin, is a naturally-derived ingredient isolated from the roots of Scutellaria baicalensis Georgi, commonly known as Huang-Qin. In traditional Chinese medicine, this substance has been used to treat allergies, inflammatory diseases and tumors (11)(12)(13). Previous studies have demonstrated that wogonin suppresses LPS-induced expression of iNOS, tumor necrosis factor-α (TNF-α), NO, and IL-1β in microglia via inhibition of NF-κB activation (14,15).…”

Section: Wogonin Protects Human Retinal Pigment Epithelium Cells Frommentioning

confidence: 99%

Wogonin protects human retinal pigment epithelium cells from LPS-induced barrier dysfunction and inflammatory responses by regulating the TLR4/NF-κB signaling pathway

Chen

Guo

2017

Molecular Medicine Reports

View full text Add to dashboard Cite

Inflammation in the retinal pigment epithelium is an important contributor to the pathogenesis of age-related macular degeneration. Wogonin is a flavonoid isolated from the root of Scutellaria baicalensis and has multiple pharmacological effects, including anti‑inflammatory effects. The present study sought to determine if the pharmacological effects of wogonin were relevant to the treatment of AMD. ARPE‑19 cells were pre‑conditioned with different concentrations of wogonin (0‑50 µM) prior to induction of inflammation with LPS (2 µg/ml). Transepithelial electrical resistance analysis demonstrated that 24 h treatment with 10 and 50 µM wogonin ameliorated LPS‑induced changes. Reverse transcription-quantitative polymerase chain reaction (RT‑qPCR) and immunoﬂuorescence analyses revealed that wogonin restrained LPS-induced tight junction proteins, claudin‑1 and ZO‑1. LPS‑induced upregulation of inflammatory mediators in ARPE‑19 cells, including IL‑1β, IL‑6, IL‑8, cyclooxygenase‑2 (COX‑2), inducible nitric oxide synthase (iNOS) and TNF‑α was reduced after pre-treatment with wogonin. In addition, RT‑qPCR and western blotting demonstrated that wogonin inhibited the expression of TLR4 in LPS‑stimulated ARPE‑19 cells. This is a novel mechanism indicating that pre‑treatment with wogonin could attenuate the TLR4/NF‑κB‑mediated inflammatory response in LPS‑stimulated ARPE‑19 cells, and thus could be a potential therapy for the treatment of AMD.

show abstract

“…Western blot analysis. cell protein extraction and western blot analysis were performed as described previously (25). Briefly, following treatment with luteolin, as described in the dNA fragmentation experiments, the total protein content of the cytosolic fraction in the supernatant was isolated from the harvested cells and measured using a BcA protein assay.…”

Section: Determination Of δψMmentioning

confidence: 99%

Luteolin induces myelodysplastic syndrome‑derived cell apoptosis via the p53‑dependent mitochondrial signaling pathway mediated by reactive oxygen species

et al. 2018

View full text Add to dashboard Cite

Luteolin, a common dietary flavonoid, induces the apoptosis of cells in several types of cancer. However, its role in myelodysplastic syndrome (MDS) and the potential underlying mechanisms remain to be elucidated. To evaluate the potential benefit and underlying mechanisms of luteolin in MDS cells, the viability of SKM‑1 cells and primary bone marrow (PBM) mononuclear cells from patients with intermediate‑ or high‑risk MDS were assessed using a Cell Counting Kit‑8 assay. The apoptotic features of cell morphology were assessed using Wright‑Giemsa staining, DNA fragmentation was analyzed by agarose gel electrophoresis, and the extent of apoptosis was quantified by flow cytometry (FCM). Reactive oxygen species (ROS) were measured by FCM with 2,7‑dichlorodihydrofluorescein diacetate staining and mitochondrial membrane potential (ΔΨm) was determined using 5,5',6,6'‑tetrachloro‑1,1',3,3'‑tetraethylbenzimidazolylcarbocyanine iodide staining. Caspase activity was detected using a fluorometric protease assay. Furthermore, the effects of luteolin on the expression of apoptosis‑related proteins were analyzed using western blot analysis. The resulting data revealed that luteolin significantly inhibited the proliferation of SKM‑1 cells in vitro, and its half maximal inhibitory concentration was 139.41 µM at 24 h and 23.95 µM at 72 h. Luteolin also markedly inhibited the proliferation of mononuclear cells from patients with intermediate‑ or high‑risk MDS. Luteolin suppressed cell proliferation, mainly as a result of the induction of apoptosis, as demonstrated by typical apoptotic morphological features, the ladder pattern of genomic DNA fragmentation, and the results of FCM using Annexin V‑FITC/PI double staining. It was also found that short‑term exposure of SKM‑1 cells to luteolin led to a marked increase in the accumulation of ROS. The increased intracellular level of ROS appeared to induce the activation of p53 and elevate the B‑cell lymphoma 2 (Bcl‑2)‑associated X protein/Bcl‑2 ratio, which modulates ΔΨm and triggers the release of cytochrome c, and may increase the activities of apoptotic protease activating factor 1, caspase‑3, ‑8 and ‑9 to further trigger the destruction of structural and specific proteins and thereby cell apoptosis. Notably, the inhibition of ROS generation by the antioxidant N‑acetyl‑L‑cysteine significantly attenuated the luteolin‑induced loss of ΔΨm and activities of caspase‑3, ‑8 and ‑9. These data suggested that luteolin exerts its pro‑apoptotic action partly through the p53‑dependent mitochondrial signaling pathway mediated by intracellular ROS, which provides a promising therapeutic candidate for patients with MDS.

show abstract

Wogonin inhibits the proliferation of myelodysplastic syndrome cells through the induction of cell cycle arrest and apoptosis

Cited by 10 publications

References 49 publications

Modulation of G2/M cell cycle arrest and apoptosis by luteolin in human colon cancer cells and xenografts

Modulation of G2/M cell cycle arrest and apoptosis by luteolin in human colon cancer cells and xenografts

Wogonin protects human retinal pigment epithelium cells from LPS-induced barrier dysfunction and inflammatory responses by regulating the TLR4/NF-κB signaling pathway

Luteolin induces myelodysplastic syndrome‑derived cell apoptosis via the p53‑dependent mitochondrial signaling pathway mediated by reactive oxygen species

Contact Info

Product

Resources

About