Luteolin exerts pro-apoptotic effect and anti-migration effects on A549 lung adenocarcinoma cells through the activation of MEK/ERK signaling pathway

Meng, Guanmin; Chai, Kequn; Li, Xinda; Zhu, Yongqiang; Huang, Weihua

doi:10.1016/j.cbi.2016.07.028

Cited by 51 publications

(36 citation statements)

References 45 publications

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“…Activation of ERK1/2 was involved in the anti-tumor resposnes in several other studies in different cancer types including lung [50, 51] although opposite reports have also been reported [52-54]. Thus, the possible dual roles of ERK signaling in terms of tumor suppressor or tumor promoter have been considered depending upon the reagents used, activity of ERK signaling, feedback loops, interaction with other kinase, and cell types studied [46].…”

Section: Discussionmentioning

confidence: 99%

Activation of ERK and Mutual Regulation of Stat3 and SP1 Contribute to Inhibition of PDK1 Expression by Atractylenolide-1 in Human Lung Cancer Cells

Xiao¹,

Zheng²,

Wu³

et al. 2017

Cell Physiol Biochem

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Background/Aims: Atractylodes macrocephula Koidz is an important ingredient in traditional Chinese herbs. One major bioactive compound, atractylenolide-1 (ATL-1), was reported to have anti-inflammatory and anti-tumor activities. However, the underlying molecular mechanism associated to this has not been well elucidated. Methods: Cell viability and cell cycle distribution were measured using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and flow cytometry assays, respectively. Western blot analysis was performed to examine the phosphorylation and protein expression of extracellular signaling-regulated kinase 1/2 (ERK1/2), signal transducer and activator of transcription 3 (Stat3), 3-phosphoinositide dependent protein kinase-1 (PDK1) and transcription factor SP1. QRT-PCR was used to examine the mRNA levels of PDK1 gene. Exogenously expressions of Stat3, PDK1 and SP1 were carried out by transient transfection assays. PDK1 promoter activity was measured by Secrete-Pair Dual Luminescence Assay Kit. A nude mice xenograft model was used to confirm the findings in vitro. Results: We showed that ATL-1 inhibited human lung cancer cell growth and induced cell cycle arrest. Furthermore, we found that ATL-1 stimulated phosphorylation of ERK1/2, inhibited phosphorylation and protein expressions of Stat3 and SP1; the latter were abrogated in the presence of MEK/ERK inhibitor PD98059. Moreover, ATL-1 reduced the protein, mRNA expression and promoter activity of PDK1. Intriguingly, exogenously expressed Stat3 and SP1 overcame ATL-1-inhibited SP1 and Stat3, and PDK1 protein expressions, respectively. Moreover, overexpression of PDK1 resisted the ATL-1-inhibited lung cancer cell growth. In consistent with the results in vitro, ATL-1 inhibited tumor growth, protein expressions of Stat3, SP1 and PDK1, and induced phosphorylation of ERK1/2 in vivo. Conclusion: In summary, our results show that ATL-1 inhibits lung cancer cell growth through activation of ERK1/2, followed by suppressing SP1 protein expression. ATL-1 also reduces phosphorylation and protein levels of Stat3. These are mutual regulation between Stat3 and SP1 proteins affected by ATL-1. This ultimately suppresses PDK1 gene expression. This study reveals a novel mechanism by which ATL-1 inhibits growth of lung cancer cells. Thus, targeting PDK1 pinpoints a potential in the lung cancer treatment.

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Section: Discussionmentioning

confidence: 99%

Activation of ERK and Mutual Regulation of Stat3 and SP1 Contribute to Inhibition of PDK1 Expression by Atractylenolide-1 in Human Lung Cancer Cells

Xiao¹,

Zheng²,

Wu³

et al. 2017

Cell Physiol Biochem

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“…[1][2][3] It has been reported to have anti-inammatory, antioxidative, antidiabetic, antimicrobial and anticancer activities in vivo. [4][5][6][7][8] Luteolin has received increasing attention due to its various biological activities and pharmacological effects and has been widely applied in the elds of medicine and functional foods.…”

Section: Introductionmentioning

confidence: 99%

Enhanced antioxidant activity, antibacterial activity and hypoglycemic effect of luteolin by complexation with manganese(ii) and its inhibition kinetics on xanthine oxidase

Dong

Yang

et al. 2017

RSC Adv.

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The present study aims to improve the biological activities of luteolin by complexation with manganese(II).UV-visible spectroscopy, infrared spectroscopy, thermogravimetric analysis and elemental analysis were adopted to assess the relevant interaction of luteolin and manganese(II) ions and the chelation sites. The antioxidant activity, hypoglycemic effect and antimicrobial activity of luteolin-manganese(II) complex with respect to its parent luteolin and the inhibition effect of which on xanthine oxidase were investigated and compared. The spectroscopic data indicated that luteolin reacts with manganese(II) cations through the chelation sites of 5-hydroxy and 4-carbonyl in two luteolin molecules. Antioxidant and antibacterial activity were enhanced after the complexation of manganese(II) cations with luteolin. An inhibition effect assay found that luteolin and luteolin-manganese(II) complex reversibly inhibited xanthine oxidase in a competitive manner. Luteolin-manganese(II) complex had a more remarkable hypoglycemic effect than luteolin by increasing the glucose consumption in liver tissue.

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“…Luteolin induced growth inhibition and apoptosis of human esophageal squamous carcinoma cell line Eca109 cells in vitro 16 . Luteolin exerts pro-apoptotic effect and anti-migration effects on A549 lung adenocarcinoma cells through the activation of MEK/ERK signaling pathway 17 . Luteolin inhibits migration of human glioblastoma U87 MG and T98G cells through downregulation of Cdc42 expression and PI3K/AKT activity 18 .…”

Section: Introductionmentioning

confidence: 99%

Luteolin exerts an anticancer effect on gastric cancer cells through multiple signaling pathways and regulating miRNAs

Pu¹,

Zhang²,

Wang³

et al. 2018

J. Cancer

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Accumulating studies confirmed that luteolin, a common dietary flavonoid which is widely distributed in plants and has diverse beneficial biological function, including anti-oxidant, anti-inflammation and anticancer properties. However, the detail mechanisms of luteolin on GC are poorly understood. Here, we investigated the anticancer effect of luteolin in GC cells in vitro and in vivo. Luteolin reduced the cell viability in a time and dose-dependent manner. Luteolin significantly inhibited cell cycle progress, colony formation, proliferation, migration, invasion and promoted apoptosis in vitro and in vivo. Luteolin also regulated these biological effects associated regulators. Mechanically, luteolin treatment regulated Notch1, PI3K, AKT, mTOR, ERK, STAT3 and P38 signaling pathways and modulated a series of miRNAs expression. These findings provide novel insight into the molecular function of luteolin which suggest its potential as a therapeutic agent for human GC.

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Luteolin exerts pro-apoptotic effect and anti-migration effects on A549 lung adenocarcinoma cells through the activation of MEK/ERK signaling pathway

Cited by 51 publications

References 45 publications

Activation of ERK and Mutual Regulation of Stat3 and SP1 Contribute to Inhibition of PDK1 Expression by Atractylenolide-1 in Human Lung Cancer Cells

Activation of ERK and Mutual Regulation of Stat3 and SP1 Contribute to Inhibition of PDK1 Expression by Atractylenolide-1 in Human Lung Cancer Cells

Enhanced antioxidant activity, antibacterial activity and hypoglycemic effect of luteolin by complexation with manganese(ii) and its inhibition kinetics on xanthine oxidase

Luteolin exerts an anticancer effect on gastric cancer cells through multiple signaling pathways and regulating miRNAs

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