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Open AccessArticle

The Novel Autophagy Inhibitor Alpha-Hederin Promoted Paclitaxel Cytotoxicity by Increasing Reactive Oxygen Species Accumulation in Non-Small Cell Lung Cancer Cells

1
Department of Biochemistry, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
2
Research Center for Integrative Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
3
Department of Pathology, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
4
School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
5
Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong SAR 999077, China
6
GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou 511436, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2018, 19(10), 3221; https://doi.org/10.3390/ijms19103221
Received: 22 September 2018 / Revised: 14 October 2018 / Accepted: 16 October 2018 / Published: 18 October 2018
Chemoresistance is a major limiting factor that impairs the outcome of non-small cell lung cancer (NSCLC) chemotherapy. Paclitaxel (Tax) induces protective autophagy in NSCLC cells, leading to the development of drug resistance. We recently identified a new autophagy inhibitor (alpha-hederin) and hypothesized that it may promote the killing effect of Tax on NSCLC cells. We found that alpha-hederin (α-Hed) could block late autophagic flux in NSCLC cells by altering lysosomal pH and inhibiting lysosomal cathepsin D maturation. Combination treatment of α-Hed and Tax synergistically reduced NSCLC cell proliferation and increased NSCLC cell apoptosis compared with treatment with α-Hed or Tax alone. Furthermore, α-Hed plus Tax enhanced the accumulation of intracellular reactive oxygen species (ROS) in NSCLC cells, while the ROS inhibitor N-acetylcysteine reversed the inhibitory effect of the combination treatment. Our findings suggest that α-Hed can increase the killing effect of Tax on NSCLC cells by promoting ROS accumulation, and that combining α-Hed with classical Tax represents a novel strategy for treating NSCLC. View Full-Text
Keywords: alpha-hederin; autophagy inhibition; non-small cell lung cancer; chemotherapy; paclitaxel; synergistic effect alpha-hederin; autophagy inhibition; non-small cell lung cancer; chemotherapy; paclitaxel; synergistic effect
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MDPI and ACS Style

Zhan, Y.; Wang, K.; Li, Q.; Zou, Y.; Chen, B.; Gong, Q.; HO, H.I.; Yin, T.; Zhang, F.; Lu, Y.; Wu, W.; Zhang, Y.; Tan, Y.; Du, B.; Liu, X.; Xiao, J. The Novel Autophagy Inhibitor Alpha-Hederin Promoted Paclitaxel Cytotoxicity by Increasing Reactive Oxygen Species Accumulation in Non-Small Cell Lung Cancer Cells. Int. J. Mol. Sci. 2018, 19, 3221. https://doi.org/10.3390/ijms19103221

AMA Style

Zhan Y, Wang K, Li Q, Zou Y, Chen B, Gong Q, HO HI, Yin T, Zhang F, Lu Y, Wu W, Zhang Y, Tan Y, Du B, Liu X, Xiao J. The Novel Autophagy Inhibitor Alpha-Hederin Promoted Paclitaxel Cytotoxicity by Increasing Reactive Oxygen Species Accumulation in Non-Small Cell Lung Cancer Cells. International Journal of Molecular Sciences. 2018; 19(10):3221. https://doi.org/10.3390/ijms19103221

Chicago/Turabian Style

Zhan, Yujuan; Wang, Kun; Li, Qiao; Zou, Yidan; Chen, Bonan; Gong, Qing; HO, Hiuting I.; Yin, Ting; Zhang, Fangyuan; Lu, Yuhua; Wu, Weijie; Zhang, Yilin; Tan, Yuhui; Du, Biaoyan; Liu, Xiaodong; Xiao, Jianyong. 2018. "The Novel Autophagy Inhibitor Alpha-Hederin Promoted Paclitaxel Cytotoxicity by Increasing Reactive Oxygen Species Accumulation in Non-Small Cell Lung Cancer Cells" Int. J. Mol. Sci. 19, no. 10: 3221. https://doi.org/10.3390/ijms19103221

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