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
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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
Zi-Chun Hua, email: firstname.lastname@example.org
Hongqin Zhuang, email: email@example.com
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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