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

doi:10.3390/ijms20010157

Paper

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

Published Jan 1, 2019 · H. Hsu, Po-Lin Liao, Yu-Wen Cheng

International Journal of Molecular Sciences

Q1 SJR score

13

Citations

0

Influential Citations

Open Access PDF Full text Semantic Scholar

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.

In Vitro Study

Study Snapshot

Chloramphenicol induces autophagy and inhibits hypoxia-inducible factor-1 alpha pathway in non-small cell lung cancer cells, suggesting potential clinical value in treating infections, inflammation, and cancer cell stemness.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

Sign up to use Study Snapshot

Consensus is limited without an account. Create an account or sign in to get more searches and use the Study Snapshot.

Create an account

Paper

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

Sign up to use Study Snapshot

References

HIF-1alpha and infectious diseases: a new frontier for the development of new therapies.

HIF-1alpha plays a significant role in inflammatory and infectious diseases, with potential for developing new therapies targeting this protein.

Old drug, new wrapping - A possible comeback for chloramphenicol?

The new liposome-in-hydrogel formulation for chloramphenicol shows promising antimicrobial activity against resistant bacteria, with potential for increased use due to its reduced toxicity.

Hypoxia and the hypoxia-regulated transcription factor HIF-1α suppress the host defence of airway epithelial cells

Hypoxia and HIF-1 suppress the innate immune response of airway epithelial cells, potentially impacting their ability to prevent and control lung infections.

SENP1 promotes hypoxia-induced cancer stemness by HIF-1α deSUMOylation and SENP1/HIF-1α positive feedback loop

Hypoxia-induced cancer stemness in HCC and hepatocarcinogenesis is exacerbated by a positive feedback loop between HIF-1 and SENP1, offering potential for novel therapeutic approaches.

Uncoupling protein 2 downregulation by hypoxia through repression of peroxisome proliferator-activated receptor γ promotes chemoresistance of non-small cell lung cancer

UCP2 downregulation in hypoxic lung cancer patients contributes to chemoresistance, suggesting potential targets for targeted therapy in chemo-refractory cases.

Citations

Synergistic Potential of Antibiotics with Cancer Treatments

Antibiotics show potential in enhancing the effectiveness of current anticancer therapies by affecting gut microbiota and cancer cells.

Progress in Lactate Metabolism and Its Regulation via Small Molecule Drugs

Small molecules targeting lactate production, transport, and lactylation show potential therapeutic potential for various diseases, including cancer, liver fibrosis, sepsis, ischemic stroke, and acute kidney injury.

Cell death and DNA damage via ROS mechanisms after applied antibiotics and antioxidants doses in prostate hyperplasia primary cell cultures

Combining antibiotics and antioxidants in prostate hyperplasia cell cultures can reduce cancer cell resistance and lead to a less aggressive cancer phenotype.

Hypoxia-associated autophagy flux dysregulation in human cancers.

Hypoxia-induced autophagy plays a crucial role in regulating tumor growth, spread, and resistance to treatment in human cancers, impacting chemoresistance and radioresistance.

Regulation of Autophagy via Carbohydrate and Lipid Metabolism in Cancer

Carbohydrate and lipid metabolism play a crucial role in regulating autophagy, which is crucial for cancer cell survival and energy production.

Leptin accelerates BMSC transformation into vertebral epiphyseal plate chondrocytes by activating SENP1‐mediated deSUMOylation of SIRT3

Leptin enhances BMSC differentiation into chondrocytes under hypoxic conditions, potentially benefiting intervertebral disc disease treatment.

Comparison of COVID-19 and Lung Cancer via Reactive Oxygen Species Signaling

Modulating reactive oxygen species signaling pathways may help alleviate mutual impacts between COVID-19 and lung cancer patients.

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

Plasma exosome-derived SENP1 is a promising prognostic biomarker for osteosarcoma patients, with higher levels indicating worse disease-free survival and overall survival outcomes.

Autophagy/ Apoptosis Induced by Geraniol through HIF-1α/BNIP3/Beclin-1 Signaling Pathway in A549 CoCl2 Treated Cells

Geraniol has an antihypoxic effect on A549 CoCl2 treated cells and induces cell death through autophagy and apoptosis through the HIF-1/BNIP3/beclin-1 signaling pathway.