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.

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

  • AIFM2 protein, human
  • Antineoplastic Agents
  • Antineoplastic Agents, Phytogenic
  • Apoptosis Regulatory Proteins
  • Drugs, Chinese Herbal
  • Mitochondrial Proteins
  • Neoplasm Proteins
  • RNA, Small Interfering
  • jinfukang
  • Cisplatin