2. Academic Validation
  3. Chloramphenicol Induces Autophagy and Inhibits the Hypoxia Inducible Factor-1 Alpha Pathway in Non-Small Cell Lung Cancer Cells

Chloramphenicol Induces Autophagy and Inhibits the Hypoxia Inducible Factor-1 Alpha Pathway in Non-Small Cell Lung Cancer Cells

  • Int J Mol Sci. 2019 Jan 3;20(1):157. doi: 10.3390/ijms20010157.
Han-Lin Hsu 1,  Po-Lin Liao 2,  Yu-Wen Cheng 3,  Shih-Hsuan Huang 4,  Chien-Hua Wu 5,  Ching-Hao Li 6,  Jaw-Jou Kang 7
Affiliations

Affiliations

  • 1 Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University-Wan Fang Hospital, Taipei 116, Taiwan. lisa11011117@gmail.com.
  • 2 Institute of Food Safety and Health Risk Assessment, School of Pharmaceutical Sciences, National Yang-Ming University, Taipei 110, Taiwan. plliao@ym.edu.tw.
  • 3 School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan. ywcheng@tmu.edu.tw.
  • 4 School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan. a001ou@gmail.com.
  • 5 Institute of Toxicology, College of Medicine, National Taiwan University, Taipei 100, Taiwan. li.elfhaha@gmail.com.
  • 6 Department of Physiology, School of Medicine; Graduate Institute of Medical Sciences, College of Medicine; Taipei Medical University, Taipei 110, Taiwan. bros22@tmu.edu.tw.
  • 7 Institute of Food Safety and Health Risk Assessment, School of Pharmaceutical Sciences, National Yang-Ming University, Taipei 112, Taiwan. jjkang@ym.edu.tw.
PMID: 30609861 DOI: 10.3390/ijms20010157
Abstract

Chloramphenicol is an inexpensive and excellent bactericidal Antibiotic. It is used to combat anaerobic infections in the Third World countries, whereas its systemic application has been abandoned in developed countries. However, in recent years, clinicians have reintroduced chloramphenicol in clinical practice. In this study, chloramphenicol was found to repress the oxygen-labile transcription factor, hypoxia inducible factor-1 alpha (HIF-1α), in hypoxic A549 and H1299 cells. Furthermore, it suppressed the mRNA levels of vascular endothelial growth factor (VEGF) and glucose transporter 1, eventually decreasing VEGF release. Chloramphenicol initiated the Autophagy pathway in treated cells, as observed by the increase in formation of Atg12-Atg5 conjugates, and in beclin-1 and LC3-II levels. The chloramphenicol-mediated HIF-1α degradation was completely reverted by autophagic flux blockage. In HIF-1α-overexpressing cells, the formation of HIF-1α/SENP-1 (Sentrin/SUMO-specific Protease 1) protein complex seemed to facilitate the escape of HIF-1α from degradation. Chloramphenicol inhibited HIF-1α/SENP-1 protein interaction, thereby destabilizing HIF-1α protein. The enhancement in HIF-1α degradation due to chloramphenicol was evident during the incubation of the Antibiotic before hypoxia and after HIF-1α accumulation. Since HIF-1α plays multiple roles in infections, inflammation, and Cancer cell stemness, our findings suggest a potential clinical value of chloramphenicol in the treatment of these conditions.

Keywords

Autophagy; Hypoxia inducible factor-1 alpha; SENP-1; chloramphenicol.

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