Fisetin, a dietary flavonoid induces apoptosis via modulating the MAPK and PI3K/Akt signalling pathways in human osteosarcoma (U-2 OS) cells

Li, Jianming; Li, Wuyin; Huang, Manyu; Zhang, Xiaoqiang

doi:10.3329/bjp.v10i4.23039

Cited by 13 publications

(7 citation statements)

References 63 publications

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“…These results suggested that P N did affect cell membrane architecture and its integrity could ultimately lead to cell death. Similar results have been obtained with another dietary flavonoid, fisetin, treatment with which resulted in loss of membrane integrity in osteocarcinoma cells [ 53 ].…”

Section: Discussionsupporting

confidence: 84%

“…High ROS production in P N -treated cells correlates well with the decreased mitochondrial membrane potential and subsequent increase in apoptosis. Li and his coworkers have also demonstrated an increase in ROS levels by fisetin leading to apoptosis in osteocarcinoma cells [ 53 ]. Similarly, Zhang et al , have demonstrated isoliensinine induced apoptosis in triple-negative human breast cancer cells through ROS generation [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

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Induction of apoptosis by pinostrobin in human cervical cancer cells: Possible mechanism of action

et al. 2018

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Pinostrobin (PN) is a naturally occurring dietary bioflavonoid, found in various medicinal herbs/plants. Though anti-cancer potential of many such similar constituents has been demonstrated, critical biochemical targets and exact mechanism for their apoptosis-inducing actions have not been fully elucidated. The present study was aimed to investigate if PN induced apoptosis in cervical cancer cells (HeLa) of human origin. It is demonstrated that PN at increasing dose effectivity reduced the cell viability as well as GSH and NO2- levels. Condensed nuclei with fragmented chromatin and changes in mitochondrial matrix morphology clearly indicated the role of mitochondria in PN induced apoptosis. A marked reduction in mitochondrial membrane potential and increased ROS production after PN treatment showed involvement of free radicals, which in turn further augment ROS levels. PN treatment resulted in DNA damage, which could have been triggered by an increase in ROS levels. Decrease in apoptotic cells in the presence of caspase 3 inhibitor in PN-treated cells suggested that PN induced apoptosis via caspase dependent pathways. Additionally, a significant increase in the expression of proteins of extrinsic (TRAIL R1/DR4, TRAIL R2/DR5, TNF RI/TNFRSF1A, FADD, Fas/TNFRSF6) and intrinsic pathway (Bad, Bax, HTRA2/Omi, SMAC/Diablo, cytochrome C, Pro-Caspase-3, Cleaved Caspase-3) was observed in the cells exposed to PN. Taken together, these observations suggest that PN efficiently induces apoptosis through ROS mediated extrinsic and intrinsic dependent signaling pathways, as well as ROS mediated mitochondrial damage in HeLa cells.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Induction of apoptosis by pinostrobin in human cervical cancer cells: Possible mechanism of action

et al. 2018

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“…Fisetin and other flavonoids have been shown to regulate cell functions, i.e., regulation of vascular smooth muscle contractility [7], protecting against hepatic steatosis [8], also has beneficial effects on anti-neurodegenerative and neuroprotective function [3]. Mechanistically, fisetin could regulate cell function by affecting several important signaling pathways, including PI3K/Akt [9,10], JAK/STAT [11,12], AMPK [8,13], and the Hippo signaling pathway [14]. Furthermore, fisetin can regulate the levels of various growth factors and proinflammatory cytokines, i.e., prostaglandin E2, tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, and IL-8 depending on the flavonoid structure and the cell types involved [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Fisetin Inhibits Osteogenic Differentiation of Mesenchymal Stem Cells via the Inhibition of YAP

et al. 2021

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Mesenchymal stem cells (MSCs) are self-renewal and capable of differentiating to various functional cell types, including osteocytes, adipocytes, myoblasts, and chondrocytes. They are, therefore, regarded as a potential source for stem cell therapy. Fisetin is a bioactive flavonoid known as an active antioxidant molecule that has been reported to inhibit cell growth in various cell types. Fisetin was shown to play a role in regulating osteogenic differentiation in animal-derived MSCs; however, its molecular mechanism is not well understood. We, therefore, studied the effect of fisetin on the biological properties of human MSCs derived from chorion tissue and its role in human osteogenesis using MSCs and osteoblast-like cells (SaOs-2) as a model. We found that fisetin inhibited proliferation, migration, and osteogenic differentiation of MSCs as well as human SaOs-2 cells. Fisetin could reduce Yes-associated protein (YAP) activity, which results in downregulation of osteogenic genes and upregulation of fibroblast genes. Further analysis using molecular docking and molecular dynamics simulations suggests that fisetin occupied the hydrophobic TEAD pocket preventing YAP from associating with TEA domain (TEAD). This finding supports the potential application of flavonoids like fisetin as a protein–protein interaction disruptor and also suggesting an implication of fisetin in regulating human osteogenesis.

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“…These data support the view that the MAPK pathway in H2O2-induced apoptosis is complex. Fisetin, a dietary flavonoid induces apoptosis via modulating the MAPK and PI3K/Akt signalling pathways in human osteosarcoma cells (Li et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Taraxerol protects the human hepatic L02 cells from hydrogen peroxide-induced apoptosis

Yao

Bai

2017

Bangladesh J Pharmacol

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Taraxerol is known to exhibit anti-inflammatory and anti-cancer activity. However, cytoprotective effect of taraxerol on hepatocytes has not been reported. In the present study, we investigated the hepatoprotective effect of taraxerol in the human hepatic L02 cells injured by hydrogen peroxide (H2O2). Taraxerol decreased H2O2-induced cell viability loss and lactate dehydrogenase release. Taraxerol also inhibited H2O2-induced cell apoptosis. Further, taraxerol attenuated H2O2-induced increase in cleaved-caspase-3 and cleaved-PARP. H2O2-activated p38 and JNK were also inhibited by taraxerol. These data suggest that taraxerol could protect the L02 cells against H2O2-induced apoptosis via suppression of p38 and JNK. Taraxerol may be an effective protective agent against oxidative stress-induced liver injury.

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Fisetin, a dietary flavonoid induces apoptosis via modulating the MAPK and PI3K/Akt signalling pathways in human osteosarcoma (U-2 OS) cells

Cited by 13 publications

References 63 publications

Induction of apoptosis by pinostrobin in human cervical cancer cells: Possible mechanism of action

Induction of apoptosis by pinostrobin in human cervical cancer cells: Possible mechanism of action

Fisetin Inhibits Osteogenic Differentiation of Mesenchymal Stem Cells via the Inhibition of YAP

Taraxerol protects the human hepatic L02 cells from hydrogen peroxide-induced apoptosis

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