Myricetin Induces Apoptosis in HepG2 Cells Through Akt/p70S6K/Bad Signaling and Mitochondrial Apoptotic Pathway

Zhang, Xiaohong; Chen, Shiyong; Tang, Lin; Shen, Ying-Zhuo; Luo, Lin; Xu, Chen-Wei; Liu, Qiong; Li, Duo

doi:10.2174/1871520613666131125123059

Cited by 52 publications

(36 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Cell apoptosis signaling pathways classified into the death receptor (extrinsic) pathway and the mitochondrial (intrinsic) pathway . The extrinsic pathways may be triggered by receptor (Fas, TRAIL, DR5, and DR4) and lead to activate caspase‐8 and caspase‐3 for inducing apoptosis or through dysfunction of mitochondria based on the ratio of proapoptotic protein (Bak or BAX)/antiapoptotic protein (Bcl‐2 or Bcl‐xl) to induce apoptosis which called the intrinsic cell apoptotic pathways . In the present study, Figure indicated that ouabain increased the activities of caspase‐8, ‐9, and ‐3, and these effects are in time‐dependently.…”

Section: Discussionsupporting

confidence: 53%

Ouabain induces apoptotic cell death in human prostate DU 145 cancer cells through DNA damage and TRAIL pathways

Chang

Shih

Chen³

et al. 2019

Environmental Toxicology

View full text Add to dashboard Cite

Ouabain, a cardiotonic steroid and specific Na+/K+‐ATPase inhibitor, has a potential to induce cancer cell apoptosis but the mechanisms of apoptosis induced by ouabain are not fully understand. The aim of this study was to investigate the cytotoxic effects of ouabain on human prostate cancer DU 145 cells in vitro. Cell morphological changes were examined by phase contrast microscopy. Cell viability, cell cycle distribution, cell apoptosis, DNA damage, the production of ROS and Ca2+, and mitochondrial membrane potential (ΔΨm) were measured by flow cytometry assay. Results indicated that ouabain induced cell morphological changes, decreased total cell viability, induced G0/G1 phase arrest, DNA damage, and cell apoptosis, increased ROS and Ca2+ production, but decreased the levels of ΔΨm in DU 145 cells. Ouabain also increased the activities of caspase‐3, ‐8, and ‐9. Western blotting was used for measuring the alterations of apoptosis‐associated protein expressions in DU 145 cells and results indicated that ouabain increased the expression of DNA damage associated proteins (pATMSer1981, p‐H2A.XSer139, and p‐p53Ser15) and ER‐stress‐associated proteins (Grp78, ATF6β, p‐PERKThr981, PERK, eIF2A, GADD153, CaMKIIβ, and caspase‐4) in time‐dependently. Furthermore, ouabain increased apoptosis‐associated proteins (DR4, DR5, Fas, Fas Ligand, and FADD), TRAIL pathway, which related to extrinsic pathway, promoted the pro‐apoptotic protein Bax, increased apoptotic‐associated proteins, such as cytochrome c, AIF, Endo G, caspase‐3, ‐8, and ‐9, but reduced anti‐apoptotic protein Bcl‐2 and Bcl‐x in DU 145 cells. In conclusion, we may suggest that ouabain decreased cell viability and induced apoptotic cell death may via caspase‐dependent and mitochondria‐dependent pathways in human prostate cancer DU 145 cells.

show abstract

Section: Discussionsupporting

confidence: 53%

Ouabain induces apoptotic cell death in human prostate DU 145 cancer cells through DNA damage and TRAIL pathways

Chang

Shih

Chen³

et al. 2019

Environmental Toxicology

View full text Add to dashboard Cite

show abstract

“…These results confirm speculation that galangin and myricetin inhibit angiogenesis in OVCAR-3 cells, at least partly, through the Akt/p70S6K/HIF-1α/VEGF pathway. Previous works found that myricetin had effects on the Akt/p70S6K pathway in HepG2 and SKH-1 cells (Jung et al, 2010; Zhang, Chen et al, 2013) and galangin inhibits the phosphorylation of Akt in HepG2 cells (Zhang, Li et al, 2013). This agrees with the results obtained in this study.…”

Section: Discussionmentioning

confidence: 95%

“…Previous studies have reported that galangin and myricetin inhibited cell growth in several cancer cells, such as hepatoma, pancreatic, esophageal, melanoma, gastric, and colon carcinoma cells (Kim, Jeon, & Nam, 2012; Kim, Ha, Yoon, & Lee, 2014; Phillips, Sangwan, Borja-Cacho, Dudeja, Vickers, & Saluja, 2011; Zang et al, 2014; Zhang et al, 2010; Zhang, Lan, Huang, & Hua, 2013; Zhang, Chen et al, 2013). However, their effects on ovarian cancer cells are currently unknown.…”

Section: Discussionmentioning

confidence: 99%

Dietary compounds galangin and myricetin suppress ovarian cancer cell angiogenesis

Huang

Chen

Rojanasakul

et al. 2015

Journal of Functional Foods

111

View full text Add to dashboard Cite

Galangin and myricetin are flavonoids isolated from vegetables and fruits which exhibit antiproliferative activity in human cancer cells. In this study, their anti-angiogenic effects were investigated with in vitro (HUVEC) and in vivo (CAM) models, which showed that galangin and myricetin inhibited angiogenesis induced by OVCAR-3 cells. The molecular mechanisms through which galangin and myricetin suppress angiogenesis were also studied. It was observed that galangin and myricetin inhibited secretion of the key angiogenesis mediator vascular endothelial growth factor (VEGF) and decreased levels of p-Akt, p-70S6K and hypoxia-inducible factor-1α (HIF-1α) proteins in A2780/CP70 and OVCAR-3 cells. Transient transfection experiments showed that galangin and myricetin inhibited secretion of VEGF by the Akt/p70S6K/ HIF-1α pathway. Moreover, a novel pathway, p21/HIF-1α/VEGF, was found to be involved in the inhibitory effect of myricetin on angiogenesis in OVCAR-3 cells. These data suggest that galangin and myricetin might serve as potential anti-angiogenic agents in the prevention of ovarian cancers dependent on new blood vessel networks.

show abstract

“…AKT can activate BAD by phosphorylation on Ser136 [20] or activate NF-κB via regulating IκB kinase (IKK) [21], thus results in anti-apoptotic effects. AKT pathway also involves in chemoresistance.…”

Section: Discussionmentioning

confidence: 99%

Insulin-Like Growth Factor 1 Receptor (IGF-1R) as a Target of MiR-497 and Plasma IGF-1R Levels Associated with TNM Stage of Pancreatic Cancer

Wang

You

et al. 2014

PLoS ONE

View full text Add to dashboard Cite

The expression levels and regulatory roles of miR-497 in pancreatic cancer are unclear. The clinical value of plasma insulin-like growth factor 1 receptor (IGF-1R) in pancreatic cancers has not been investigated. In the present study, we demonstrated that miR-497 was significantly downregulated in pancreatic cancer tissues. Upregulation of miR-497 in BxPC-3 and AsPC-1 pancreatic cancer cell lines inhibited proliferation, enhanced apoptosis, re-sensitized cells to gemcitabine and suppressed IGF-1R and p-AKT expression through direct downregulation of IGF-1R protein expression. Opposite effects were observed after downregulation of miR-497. Plasma IGF-1R levels in patients with pancreatic cancer increased significantly, compared with that in patients with chronic pancreatitis, other pancreatic tumors and pancreatic neuroendocrine tumors (P = 0.006, P = 0.018 and P = 0.004, respectively), and displayed potential values for distinguishing pancreatic lesions. However, the levels in pancreatic cancer patients were comparable to that in healthy volunteers (P = 0.095). The tumor locations and TNM stage were associated with plasma IGF-1R levels (P = 0.013 and P = 0.01, respectively). There was no significant difference of overall survival between high and low IGF-1R expression groups. In conclusion, we demonstrated that miR-497 attenuated the malignancy of pancreatic cancer cells and promoted sensitivity of cells to gemcitabine by directly downregulation of IGF-1R expression. Plasma IGF-1R displayed a potential value for distinguishing pancreatic lesions and could be a new biomarker for guiding TNM stage of pancreatic cancer.

show abstract

Myricetin Induces Apoptosis in HepG2 Cells Through Akt/p70S6K/Bad Signaling and Mitochondrial Apoptotic Pathway

Cited by 52 publications

References 34 publications

Ouabain induces apoptotic cell death in human prostate DU 145 cancer cells through DNA damage and TRAIL pathways

Ouabain induces apoptotic cell death in human prostate DU 145 cancer cells through DNA damage and TRAIL pathways

Dietary compounds galangin and myricetin suppress ovarian cancer cell angiogenesis

Insulin-Like Growth Factor 1 Receptor (IGF-1R) as a Target of MiR-497 and Plasma IGF-1R Levels Associated with TNM Stage of Pancreatic Cancer

Contact Info

Product

Resources

About