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

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.

Autophagy Induction by a Small Molecule Inhibits Salmonella Survival in Macrophages and Mice

“…The antibiotic chloramphenicol inhibits the bacterial 50S ribosomal subunit and also induces autophagy in eukaryotic cells (37–41). We therefore sought to determine whether D61 may act in synergy with chloramphenicol against Salmonella in primary macrophages.…”

Inhaled gold nanoparticles cause cerebral edema and upregulate endothelial aquaporin 1 expression, involving caveolin 1 dependent repression of extracellular regulated protein kinase activity

“…The cytotoxic potential of Au-NPs was assayed by the conversion of 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) to insoluble formazan [61] .…”

“…bEnd.3 cells grown on 60-mm dishes treated with Au-NPs at prescribed periods, for example, 3~24 h for AQP1 protein analysis and 10~60 min for kinase phosphorylation analysis. After treatment, cell whole lysates were prepared as described [61] . Protein samples were separated by SDS-PAGE and electro transferred onto PVDF membranes.…”

Plasma Exosome-Derived Sentrin SUMO-Specific Protease 1: A Prognostic Biomarker in Patients With Osteosarcoma

“…SENP1 is an important member of the enzyme protein family that regulates the reverse reaction of SUMO modification ( 27 ). Previous studies have shown that SENP1 plays an important role in the occurrence and progression of malignant tumors by regulating hypoxia-inducible factor (HIF)-1α ( 28 , 29 ). SENP1 is the regulatory target gene of HIF-1α.…”