Engeletin suppresses lung cancer progression by inducing apoptotic cell death through modulating the XIAP signaling pathway: A molecular mechanism involving ER stress

Liu, Ting; Li, Yang; Sun, Jiaolin; Tian, Gang; Shi, Zhihong

doi:10.1016/j.biopha.2020.110221

Cited by 18 publications

(10 citation statements)

References 60 publications

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“…Engeletin, which is also referred to as rhamnoside of dihydrokaempferol, is a bioactive derivative of Smilax glabra rhizomilax . In prior research, engeletin has shown anti-inflammatory and antioxidant activity in vitro ( 15 ) and ability to further suppress the growth of cervical and lung cancer cells ( 16 , 17 ). Herein, we explored the protective activity of engeletin in the context of CI/R injury and assessed the underlying mechanisms whereby it regulates angiogenesis.…”

Section: Introductionmentioning

confidence: 99%

Engeletin protects against cerebral ischemia/reperfusion injury by modulating the VEGF/vasohibin and Ang-1/Tie-2 pathways

Liu

et al. 2021

Braz J Med Biol Res

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Engeletin is a natural derivative of Smilax glabra rhizomilax that exhibits anti-inflammatory activity and suppresses lipid peroxidation. In the present study, we sought to elucidate the mechanistic basis for the neuroprotective and pro-angiogenic activity of engeltin in a human umbilical vein endothelial cells (HUVECs) oxygen-glucose deprivation and reoxygenation (OGD/R) model system and a middle cerebral artery occlusion (MCAO) rat model of cerebral ischemia and reperfusion injury. These analyses revealed that engeletin (10, 20, or 40 mg/kg) was able to reduce the infarct volume, increase cerebral blood flow, improve neurological function, and bolster the expression of vascular endothelial growth factor (VEGF), vasohibin-2 (Vash-2), angiopoietin-1 (Ang-1), phosphorylated human angiopoietin receptor tyrosine kinase 2 (p-Tie2), and platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) in MCAO rats. Similarly, engeletin (100, 200, or 400 nM) markedly enhanced the migration, tube formation, and VEGF expression of HUVECs in an OGD/R model system, while the VEGF receptor (R) inhibitor axitinib reversed the observed changes in HUVEC tube formation activity and Vash-2, VEGF, and CD31 expression. These data suggested that engeletin exhibited significant neuroprotective effects against cerebral ischemia and reperfusion injury in rats, and improved cerebrovascular angiogenesis by modulating the VEGF/vasohibin and Ang-1/Tie-2 pathways.

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Section: Introductionmentioning

confidence: 99%

Engeletin protects against cerebral ischemia/reperfusion injury by modulating the VEGF/vasohibin and Ang-1/Tie-2 pathways

Liu

et al. 2021

Braz J Med Biol Res

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“…In addition, the candidate metabolites were further screened using FC > 1.5, p < 0.05 and VIP > 1 as selection criteria, and six compounds, including quercetin 3‐O‐glucuronide [36], engeletin [37], alstilbin [38], terpinen‐4‐ol [39], alpha‐mangostin [40], and matrine [41] were selected. The classifications of the 18 reported potential antitumor compounds are shown in Table 1.…”

Section: Resultsmentioning

confidence: 99%

Global regulatory factor AaLaeA upregulates the production of antitumor substances in the endophytic fungus Alternaria alstroemeria

et al. 2022

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The global regulatory factor LaeA has been shown to be involved in the biosynthesis of secondary metabolites in various fungi. In a previous work, we isolated an endophytic fungus from Artemisia annua, and its extract had a significant inhibitory effect on the A549 cancer cell line. Phylogenetic analysis further identified the strain as Alternaria alstroemeria. Overexpression of AalaeA gene resulted in significantly increased antitumor activity of this strain's extract. The 3‐(4, 5‐ dimethylthiazol‐2‐yl)‐2, 5‐diphenyltetrazolium bromide assay results showed that the inhibition rate of the AalaeAOE29 mutant extract on A549 cancer cells was significantly higher than that of the WT extract, as the IC50 decreased from 195.0 to 107.4 μg/ml, and the total apoptosis rate was enhanced. Overexpression of the AalaeA gene significantly increased the contents of myricetin, geraniol, ergosterol, and 18 other antitumor compounds as determined by metabolomic analysis. Transcriptomic analysis revealed significant changes in 95 genes in the mutant strain, including polyketide synthases, nonribosomal peptide synthases, cytochrome P450s, glycosyltransferases, acetyl‐CoA acetyltransferases, and others. These results suggested that AaLaeA mediated the antitumor activity of the metabolites in A. alstroemeria by regulating multiple metabolic pathways.

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“…Pharmacological studies have demonstrated that the active compounds in Smilax glabra Roxb possess various pharmacological effects, such as anti-infective, 20 anti-cancer, 21 anti-inflammatory, 22 , 23 antioxidant, 24 , 24 and cardiovascular protective activities. 26 , 27 Engeletin (Eng) is a dihydroflavonoid extracted from Smilax glabra Roxb . and it possesses a wide range of pharmacological effects.…”

Section: Introductionmentioning

confidence: 99%

The Molecular Mechanisms Study of Engeletin Suppresses RANKL-Induced Osteoclastogenesis and Inhibits Ovariectomized Murine Model Bone Loss

Feng,

Liu,

Wang

et al. 2023

JIR

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Objective Osteoclastogenesis, the process of osteoclast differentiation, plays a critical role in bone homeostasis. Overexpression of osteoclastogenesis can lead to pathological conditions, such as osteoporosis and osteolysis. This study aims to investigate the role of Engelitin in the process of RAW264.7 cell differentiation into osteoclasts induced by RANKL, as well as in a mouse model of bone loss following ovariectomy. Methods We used RANKL-stimulated RAW264.7 cells as an in vitro osteoclast differentiation model. The effects of Eng on morphological changes during osteoclast differentiation were evaluated using TRAP and F-actin staining. The effects of Eng on the molecular level of osteoclast differentiation were evaluated using Western blot and q-PCR. The level of reactive oxygen species was evaluated using the DCFH-DA staining method. We then used ovariectomized mice as a bone loss animal model. The effects of Eng on changes in bone loss in vivo were evaluated using micro-CT and histological analysis staining. Results In the in vitro experiments, Eng exhibited dose-dependent inhibition of osteoclast formation and F-actin formation. At the molecular level, Eng dose-dependently suppressed the expression of specific RNAs (NFATc1, c-Fos, TRAP, Cathepsin K, MMP-9) involved in osteoclast differentiation, and inhibited the phosphorylation of proteins such as IκBα, P65, ERK, JNK, and P38. Additionally, Eng dose-dependently suppressed ROS levels and promoted the expression of antioxidant enzymes such as Nrf2, HO-1, and NQO1. In the in vivo experiments, Eng improved bone loss in ovariectomized mice. Conclusion Our study found that Eng inhibited RANKL-induced osteoclast differentiation through multiple signaling pathways, including MAPKs, NF-κB, and ROS aggregation. Furthermore, Eng improved bone loss in ovariectomized mice.

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Engeletin suppresses lung cancer progression by inducing apoptotic cell death through modulating the XIAP signaling pathway: A molecular mechanism involving ER stress

Cited by 18 publications

References 60 publications

Engeletin protects against cerebral ischemia/reperfusion injury by modulating the VEGF/vasohibin and Ang-1/Tie-2 pathways

Engeletin protects against cerebral ischemia/reperfusion injury by modulating the VEGF/vasohibin and Ang-1/Tie-2 pathways

Global regulatory factor AaLaeA upregulates the production of antitumor substances in the endophytic fungus Alternaria alstroemeria

The Molecular Mechanisms Study of Engeletin Suppresses RANKL-Induced Osteoclastogenesis and Inhibits Ovariectomized Murine Model Bone Loss

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