Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress

Jun Lu; Jian Chen; Nianjun Xu; Jun Wu; Yani Kang; Tingting Shen; Hualei Kong; Chao Ma; Ming Cheng; Zhifeng Shao; Ling Xu; Xiaodong Zhao

doi:10.1016/j.toxlet.2016.07.002

Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress

Toxicol Lett. 2016 Sep 6:258:227-236. doi: 10.1016/j.toxlet.2016.07.002. Epub 2016 Jul 5.

Authors

Jun Lu¹, Jian Chen², Nianjun Xu³, Jun Wu⁴, Yani Kang⁵, Tingting Shen⁶, Hualei Kong⁷, Chao Ma⁸, Ming Cheng⁹, Zhifeng Shao¹⁰, Ling Xu¹¹, Xiaodong Zhao¹²

Affiliations

¹ Shanghai Center for Systems Biomedicine, School of Biomedical Engineering and Bio-ID Center, Shanghai Jiao Tong University, 800 Dongchuan Rd., Shanghai 200240, China. Electronic address: lujun512@yahoo.com.
² Shanghai Center for Systems Biomedicine, School of Biomedical Engineering and Bio-ID Center, Shanghai Jiao Tong University, 800 Dongchuan Rd., Shanghai 200240, China. Electronic address: cjcchengjian@126.com.
³ Laboratory of Marine Biotechnology of Zhejiang Province, School of Marine Sciences, Ningbo University, Ningbo, Zhejiang 315211, China. Electronic address: xunianjun@nbu.edu.dn.
⁴ Shanghai Center for Systems Biomedicine, School of Biomedical Engineering and Bio-ID Center, Shanghai Jiao Tong University, 800 Dongchuan Rd., Shanghai 200240, China. Electronic address: junwu302@gmail.com.
⁵ Shanghai Center for Systems Biomedicine, School of Biomedical Engineering and Bio-ID Center, Shanghai Jiao Tong University, 800 Dongchuan Rd., Shanghai 200240, China. Electronic address: kangyani@sjtu.edu.cn.
⁶ Shanghai Center for Systems Biomedicine, School of Biomedical Engineering and Bio-ID Center, Shanghai Jiao Tong University, 800 Dongchuan Rd., Shanghai 200240, China. Electronic address: talentanan@126.com.
⁷ Shanghai Center for Systems Biomedicine, School of Biomedical Engineering and Bio-ID Center, Shanghai Jiao Tong University, 800 Dongchuan Rd., Shanghai 200240, China. Electronic address: khl0798@163.com.
⁸ Tumor Institute of Traditional Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 725 South Wanping Rd., Shanghai 200032, China. Electronic address: marshallshutcm@163.com.
⁹ Shanghai Center for Systems Biomedicine, School of Biomedical Engineering and Bio-ID Center, Shanghai Jiao Tong University, 800 Dongchuan Rd., Shanghai 200240, China. Electronic address: mingcheng@sjtu.edu.cn.
¹⁰ Shanghai Center for Systems Biomedicine, School of Biomedical Engineering and Bio-ID Center, Shanghai Jiao Tong University, 800 Dongchuan Rd., Shanghai 200240, China. Electronic address: zs9q@virginia.edu.
¹¹ Tumor Institute of Traditional Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 725 South Wanping Rd., Shanghai 200032, China; Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, 110 Ganhe Rd., Shanghai 200437, China. Electronic address: xulq67@aliyun.com.
¹² Shanghai Center for Systems Biomedicine, School of Biomedical Engineering and Bio-ID Center, Shanghai Jiao Tong University, 800 Dongchuan Rd., Shanghai 200240, China; Tumor Institute of Traditional Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 725 South Wanping Rd., Shanghai 200032, China. Electronic address: xiaodongzhao@sjtu.edu.cn.

PMID: 27392435
DOI: 10.1016/j.toxlet.2016.07.002

Abstract

Application of cisplatin (DDP) for treating lung cancer is restricted due to its toxicity and lung cancer's drug resistance. In this study, we examined the effect of Jinfukang (JFK), an effective herbal medicine against lung cancer, on DDP-induced cytotoxicity in lung cancer cells. Morphologically, we observed that JFK increases DDP-induced pro-apoptosis in A549 cells in a synergistic manner. Transcriptome profiling analysis indicated that the combination of JFK and DDP regulates genes involved in apoptosis-related signaling pathways. Moreover, we found that the combination of JFK and DDP produces synergistic pro-apoptosis effect in other lung cancer cell lines, such as NCI-H1975, NCI-H1650, and NCI-H2228. Particularly, we demonstrated that AIFM2 is activated by the combined treatment of JFK and DDP and partially mediates the synergistic pro-apoptosis effect. Collectively, this study not only offered the first evidence that JFK promotes DDP-induced cytotoxicity, and activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress, but also provided a novel insight for improving cytotoxicity by combining JFK with DDP to treat lung cancer cells.

Keywords: AIFM2; Apoptosis; Cisplatin; Cytotoxicity; Jinfukang; Lung cancer; Transcriptome.

MeSH terms

A549 Cells
Adenocarcinoma, Bronchiolo-Alveolar / drug therapy
Adenocarcinoma, Bronchiolo-Alveolar / metabolism
Antineoplastic Agents / pharmacology
Antineoplastic Agents, Phytogenic / pharmacology*
Antineoplastic Combined Chemotherapy Protocols / pharmacology*
Apoptosis / drug effects*
Apoptosis Regulatory Proteins / agonists*
Apoptosis Regulatory Proteins / antagonists & inhibitors
Apoptosis Regulatory Proteins / genetics
Apoptosis Regulatory Proteins / metabolism
Cell Line, Tumor
Cisplatin / pharmacology
Drug Resistance, Neoplasm
Drug Synergism
Drugs, Chinese Herbal / pharmacology*
Gene Expression Profiling
Gene Expression Regulation, Neoplastic / drug effects
Gene Regulatory Networks / drug effects
Humans
Lung Neoplasms / drug therapy*
Lung Neoplasms / metabolism
Mitochondrial Proteins / agonists*
Mitochondrial Proteins / antagonists & inhibitors
Mitochondrial Proteins / genetics
Mitochondrial Proteins / metabolism
Neoplasm Proteins / agonists*
Neoplasm Proteins / antagonists & inhibitors
Neoplasm Proteins / genetics
Neoplasm Proteins / metabolism
RNA Interference
RNA, Small Interfering

Substances

ferroptosis suppressor protein 1, human
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Apoptosis Regulatory Proteins
Drugs, Chinese Herbal
Mitochondrial Proteins
Neoplasm Proteins
RNA, Small Interfering
jinfukang
Cisplatin