Research Papers:

Astragalin-induced cell death is caspase-dependent and enhances the susceptibility of lung cancer cells to tumor necrosis factor by inhibiting the NF-кB pathway

Minghui Chen _, Fangfang Cai, Daolong Zha, Xueshi Wang, Wenjing Zhang, Yan He, Qilai Huang, Hongqin Zhuang and Zi-Chun Hua

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Oncotarget. 2017; 8:26941-26958. https://doi.org/10.18632/oncotarget.15264

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Minghui Chen1,2,*, Fangfang Cai1,*, Daolong Zha1, Xueshi Wang1, Wenjing Zhang2, Yan He2, Qilai Huang2,3, Hongqin Zhuang1,3, Zi-Chun Hua1,2,4

1The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China

2State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau

3Changzhou High-Tech Research Institute of Nanjing University and Target Pharma Laboratory, Changzhou, Jiangsu, China

4College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China

*These authors have contributed equally to this work

Correspondence to:

Zi-Chun Hua, email: [email protected]

Hongqin Zhuang, email: [email protected]

Keywords: natural compounds, astragalin, apoptosis, non-small cell lung cancer, tumor therapy

Received: June 13, 2016    Accepted: January 22, 2017    Published: February 10, 2017


Flavonoids are naturally occurring polyphenolic compounds and are among the most promising anticancer agents. Here, we demonstrate that the flavonoid astragalin (AG), also known as kaempferol-3-O-β-D-glucoside, induces cell death. This was prevented by the caspase inhibitors z-DEVD-FMK and z-LEHD-FMK. AG-induced cell death was associated with an increase in the Bax:Bcl-2 ratio and amplified by the inhibition of extracellular signal-regulated kinase (ERK)-1/2 and Akt signaling. Meanwhile, AG suppressed LPS-induced NF-κB activation. Additional studies revealed that AG inhibited tumor necrosis factor-alpha (TNFα)-induced NF-κB activity. AG also potentiated TNFα-induced apoptosis in A549 cells. Furthermore, using a mouse xenograft model, we demonstrated that AG suppressed tumor growth and induced cancer cell apoptosis in vivo. Taken together, these results suggest that AG may be a promising cancer therapeutic drug that warrants further investigation into its potential clinical applications.

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