J Cancer 2021; 12(13):4075-4085. doi:10.7150/jca.57054 This issue Cite

Research Paper

Artemisinin Derivatives Inhibit Non-small Cell Lung Cancer Cells Through Induction of ROS-dependent Apoptosis/Ferroptosis

Qiuting Zhang1,2,3, Huimei Yi1,2, Hui Yao1,2, Lu Lu1,2, Guangchun He1,2, Mi Wu1,2, Chanjuan Zheng1,2, Ying Li1,2, Sisi Chen1,2, Lewei Li3, Hongyuan Yu3, Guifei Li1, Xiaojun Tao3✉, Shujun Fu1,2✉, Xiyun Deng1,2✉

1. Key Laboratory of Translational Cancer Stem Cell Research, Hunan Normal University, Changsha, Hunan 410013, China.
2. Departments of Pathology and Pathophysiology, Hunan Normal University School of Medicine, Changsha, Hunan 410013, China.
3. Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, School of Medicine, Hunan Normal University, Changsha 410013, China.

Citation:
Zhang Q, Yi H, Yao H, Lu L, He G, Wu M, Zheng C, Li Y, Chen S, Li L, Yu H, Li G, Tao X, Fu S, Deng X. Artemisinin Derivatives Inhibit Non-small Cell Lung Cancer Cells Through Induction of ROS-dependent Apoptosis/Ferroptosis. J Cancer 2021; 12(13):4075-4085. doi:10.7150/jca.57054. https://www.jcancer.org/v12p4075.htm
Other styles

File import instruction

Abstract

Graphic abstract

Non-small cell lung cancer (NSCLC) is one of the major cancer-related causes of morbidity and mortality worldwide. Despite the progress in lung cancer treatment, there is still an urgent need to discover novel therapeutic agents for NSCLC. Natural products represent a rich source of bioactive compounds. Through a natural compound library screening assay, we found that a group of anti-insect drugs had significant inhibitory effect on the proliferation of NSCLC cells. Among the anti-insect drugs, two derivatives of artemisinin, i.e., artesunate (ART) and dihydroartemisinin (DHA), a group of well-known anti-malarial drugs, have been shown to possess selective anti-cancer properties. Mechanistically, we found that ART and DHA induced apoptosis of A549 cells as evidenced by decreased protein level of VDAC and increased caspase 3 cleavage. Furthermore, cystine/glutamate transporter (xCT), a core negative regulator of ferroptosis, was downregulated by ART and DHA. The mRNA level of transferrin receptor (TFRC), a positive regulator of ferroptosis, was upregulated by ART and DHA. ART/DHA-induced apoptosis and ferroptosis in NSCLC cells were partly reversed by N-Acetyl-L-cysteine (NAC), a ROS scavenger, and ferrostatin-1, a ferroptosis inhibitor, respectively. These results suggest that artemisinin derivatives have anti-NSCLC activity through induction of ROS-dependent apoptosis/ferroptosis. Our findings provide the experimental basis for the potential application of artemisinin derivatives as a class of novel therapeutic drugs for NSCLC.

Keywords: Non-small cell lung cancer, Artemisinin derivatives, Ferroptosis, Apoptosis, Caner therapy.


Citation styles

APA
Zhang, Q., Yi, H., Yao, H., Lu, L., He, G., Wu, M., Zheng, C., Li, Y., Chen, S., Li, L., Yu, H., Li, G., Tao, X., Fu, S., Deng, X. (2021). Artemisinin Derivatives Inhibit Non-small Cell Lung Cancer Cells Through Induction of ROS-dependent Apoptosis/Ferroptosis. Journal of Cancer, 12(13), 4075-4085. https://doi.org/10.7150/jca.57054.

ACS
Zhang, Q.; Yi, H.; Yao, H.; Lu, L.; He, G.; Wu, M.; Zheng, C.; Li, Y.; Chen, S.; Li, L.; Yu, H.; Li, G.; Tao, X.; Fu, S.; Deng, X. Artemisinin Derivatives Inhibit Non-small Cell Lung Cancer Cells Through Induction of ROS-dependent Apoptosis/Ferroptosis. J. Cancer 2021, 12 (13), 4075-4085. DOI: 10.7150/jca.57054.

NLM
Zhang Q, Yi H, Yao H, Lu L, He G, Wu M, Zheng C, Li Y, Chen S, Li L, Yu H, Li G, Tao X, Fu S, Deng X. Artemisinin Derivatives Inhibit Non-small Cell Lung Cancer Cells Through Induction of ROS-dependent Apoptosis/Ferroptosis. J Cancer 2021; 12(13):4075-4085. doi:10.7150/jca.57054. https://www.jcancer.org/v12p4075.htm

CSE
Zhang Q, Yi H, Yao H, Lu L, He G, Wu M, Zheng C, Li Y, Chen S, Li L, Yu H, Li G, Tao X, Fu S, Deng X. 2021. Artemisinin Derivatives Inhibit Non-small Cell Lung Cancer Cells Through Induction of ROS-dependent Apoptosis/Ferroptosis. J Cancer. 12(13):4075-4085.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Popup Image