Reactive oxygen species-mediated mitochondrial pathway is involved in Baohuoside I-induced apoptosis in human non-small cell lung cancer

Song, Jie; Shu, Luan; Zhang, Zhenhai; Tan, Xuecai; Sun, E; Jin, Xin; Chen, Yan; Jia, Xiao‐Bin

doi:10.1016/j.cbi.2012.05.005

Cited by 56 publications

(50 citation statements)

References 31 publications

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“…Immunofluorescence assay was performed as previously described (16). In brief, cultured cells grown on plastic chamber slides were fixed in 4% formaldehyde for 30 min at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Nobiletin inhibits epithelial-mesenchymal transition of human non-small cell lung cancer cells by antagonizing the TGF-β1/Smad3 signaling pathway

Chen

Liu

et al. 2016

Oncology Reports

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Abstract. Epithelial-mesenchymal transition (EMT) is a critical cellular process in cancer metastasis, during which epithelial polarized cells become motile mesenchymal cells. Since transforming growth factor-β (TGF-β) is a potent inducer of EMT, blocking of TGF-β/Smad signaling has become a promising cancer therapy. Nobiletin, a polymethoxy flavonoid from Citrus depressa, has been shown to be valuable for cancer treatment, yet the mechanism remains unclear. In the present study, lung adenocarcinoma A549 and H1299 cells were used to evaluate the effect of nobiletin on EMT induced by TGF-β1. Nobiletin successfully inhibited TGF-β1-induced EMT, migration, invasion and adhesion in vitro, accompanied by attenuation of MMP-2, MMP-9, p-Src, p-FAK, p-paxillin, Snail, Slug, Twist and ZEB1 expression. Nobiletin inhibited the transcriptional activity of Smads without changing the phosphorylation status or translocation of Smads induced by TGF-β1. Moreover, Smad3 is requisite in TGF-β1-stimulated EMT. Smad3 overexpression meaningfully impaired the ability of nobiletin to reverse TGF-β1-induced EMT. In vivo, nobiletin prohibited the growth of metastatic nodules in the lungs of nude mice. Moreover, nobiletin inhibited tumor growth and reversed EMT in mice bearing A549-Luc xenografts, as revealed by IVIS imaging and immunohistochemical analysis. Collectively, the data suggest that nobiletin prevents EMT by inactivating TGF-β1/Smad3 signaling.

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“…Immunofluorescence assay was performed as previously described (16). In brief, cultured cells grown on plastic chamber slides were fixed in 4% formaldehyde for 30 min at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Nobiletin inhibits epithelial-mesenchymal transition of human non-small cell lung cancer cells by antagonizing the TGF-β1/Smad3 signaling pathway

Chen

Liu

et al. 2016

Oncology Reports

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“…When tumors reached an acceptable size, DiR-M was injected into the tail vein of the tumor-bearing mice at a dose of 5.0 mg/kg to investigate the in vivo distribution. The mice were anesthetized and imaged at predetermined time points (2,4,8,12, and 24 hours) after intravenous injection using the Maestro in vivo imaging system (NightOWL II LB983; Berthold Technologies, Bad Wildbad, Germany).…”

Section: In Vivo Imagingmentioning

confidence: 99%

“…[1][2][3] Baohuoside I can induce apoptosis in human non-small-cell lung cancer (NSCLC) cells via reactive oxygen species-mediated mitochondrial pathway and also inhibits the growth of U266 multiple myeloma and preosteoclastic RAW264.7 cells. [4][5][6][7] Baohuoside I has very poor solubility in water. Moreover, baohuoside I possesses a low absorptive permeability and a high rate of efflux via apical efflux transporters such as multidrug resistance-associated proteins 1 and 2 (MRP 1 and MRP 2) and P-glycoprotein (P-gp).…”

Section: Introductionmentioning

confidence: 99%

D-α-Tocopheryl polyethylene glycol succinate/Solutol HS 15 mixed micelles for the delivery of baohuoside I against non-small-cell lung cancer: optimization and in vitro, in vivo evaluation

Yan¹,

Zhang²,

Jia³

et al. 2016

IJN

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Baohuoside I, extracted from the Herba epimedii, is an effective but a poorly soluble antitumor drug. To improve its solubility, formulation of baohuoside I-loaded mixed micelles with d -α-tocopheryl polyethylene glycol succinate and Solutol HS 15 (BTSM) has been developed in this study. We performed a systematic comparative evaluation of the antiproliferative effect, cellular uptake, antitumor efficacy, and in vivo tumor targeting of these micelles using non-small-cell lung cancer (NSCLC) A549 cells. Results showed that the obtained micelles have a mean particle size of ~62.54 nm, and the size of micelles was narrowly distributed. With the improved cellular uptake, BTSM displayed a more potent anti-proliferative action on A549 cell lines than baohuoside I; half-maximal inhibitory concentration was 7.83 vs 20.37 µg/mL, respectively. The antitumor efficacy test in nude mice showed that BTSM exhibited significantly higher antitumor activity against NSCLC with lesser toxic effects on normal tissues. The imaging study for in vivo targeting demonstrated that the mixed micelles formulation achieved effective and targeted drug delivery. Therefore, BTSM might be a potential antitumor formulation.

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“…Baohuoside I (also known as icariside II) is the main active flavonoid component of H. epimedii (Qian et al, 2012;Zhai et al, 2013;Yu et al, 2013;Xiao et al, 2014). Baohuoside I can induce apoptosis in human non-small cell lung cancer cells (NSCLC) via reactive oxygen speciesmediated mitochondrial pathway and also inhibits the growths of U266 multiple myeloma and pre-osteoclastic RAW264.7 cells (Choi et al, 2008;Kim et al, 2011;Jin et al, 2012a;Song et al, 2012;Liu et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Optimization and anticancer activity in vitro and in vivo of baohuoside I incorporated into mixed micelles based on lecithin and Solutol HS 15

et al. 2015

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Baohuoside I, extracted from the Herba epimedii, is an effective but a poorly soluble antitumor drug. To improve its solubility, formulation of baohuoside I-loaded mixed micelles with lecithin and Solutol HS 15 (BLSM) has been performed in this study. We performed a systematic comparative evaluation of the antiproliferative effect, cellular uptake, antitumor efficacy, and in vivo tumor targeting of these micelles using non-small cell lung cancer (NSCLC) A549 cells.Results showed that the obtained micelles have a mean particle size of around 62.54 nm, and the size of micelles was narrowly distributed. With the improved cellular uptake, BLSM displayed a more potent antiproliferative action on A549 cell lines than baohuoside I; halfmaximal inhibitory concentration (IC 50 ) was 6.31 versus 18.28 mg/mL, respectively. The antitumor efficacy test in nude mice showed that BLSM exhibited significantly higher antitumor activity against NSCLC with lesser toxic effects on normal tissues. The imaging study for in vivo targeting demonstrated that the mixed micelles formulation achieved effective and targeted drug delivery. Therefore, BLSM might be a potential antitumor formulation.

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Reactive oxygen species-mediated mitochondrial pathway is involved in Baohuoside I-induced apoptosis in human non-small cell lung cancer

Cited by 56 publications

References 31 publications

Nobiletin inhibits epithelial-mesenchymal transition of human non-small cell lung cancer cells by antagonizing the TGF-β1/Smad3 signaling pathway

Nobiletin inhibits epithelial-mesenchymal transition of human non-small cell lung cancer cells by antagonizing the TGF-β1/Smad3 signaling pathway

D-α-Tocopheryl polyethylene glycol succinate/Solutol HS 15 mixed micelles for the delivery of baohuoside I against non-small-cell lung cancer: optimization and in vitro, in vivo evaluation

Optimization and anticancer activity in vitro and in vivo of baohuoside I incorporated into mixed micelles based on lecithin and Solutol HS 15

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Reactive oxygen species-mediated mitochondrial pathway is involved in Baohuoside I-induced apoptosis in human non-small cell lung cancer

Cited by 56 publications

References 31 publications

Nobiletin inhibits epithelial-mesenchymal transition of human non-small cell lung cancer cells by antagonizing the TGF-β1/Smad3 signaling pathway

Nobiletin inhibits epithelial-mesenchymal transition of human non-small cell lung cancer cells by antagonizing the TGF-β1/Smad3 signaling pathway

D-&alpha;-Tocopheryl polyethylene glycol succinate/Solutol HS 15 mixed micelles for the delivery of baohuoside I against non-small-cell lung cancer: optimization and in vitro, in vivo evaluation

Optimization and anticancer activity in vitro and in vivo of baohuoside I incorporated into mixed micelles based on lecithin and Solutol HS 15

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D-α-Tocopheryl polyethylene glycol succinate/Solutol HS 15 mixed micelles for the delivery of baohuoside I against non-small-cell lung cancer: optimization and in vitro, in vivo evaluation