A Novel Use of Gentamicin in the ROS-Mediated Sensitization of NCI-H460 Lung Cancer Cells to Various Anticancer Agents

• Published in: ACS chemical biology Vol. 8; no. 12; pp. 2771 - 2777
• Main Authors: Cuccarese, Michael F, Singh, Amit, Amiji, Mansoor, O’Doherty, George A
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 20-12-2013
• Subjects: Antibiotics, Antineoplastic - chemistry; Antibiotics, Antineoplastic - pharmacology; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - pharmacology; Camptothecin - chemistry; Camptothecin - pharmacology; Cell Line, Tumor; Cell Survival - drug effects; Digitoxin - chemistry; Digitoxin - pharmacology; Drug Synergism; Gentamicins - chemistry; Gentamicins - pharmacology; High-Throughput Screening Assays; Humans; Reactive Oxygen Species - chemistry; Reactive Oxygen Species - metabolism; Vinblastine - chemistry; Vinblastine - pharmacology
• ISSN: 1554-8929; 1554-8937
• DOI: 10.1021/cb4007024

Aminoglycosides are broad-spectrum antibiotics that are used for the treatment of severe Gram-negative and Gram-positive bacterial infections. While bactericidal effects of aminoglycosides are due to binding to the 30S subunit of the bacterial ribosome, aminoglycosides can affect protein synthesis, intracellular calcium levels, and levels of reactive oxygen species (ROS) in eukaryotic cells. While aminoglycosides can be cytotoxic at high concentrations, our results show that at much lower doses, gentamicin can be implemented as a sensitizing agent for the NSCLC cell line NCI-H460, increasing the efficacy of camptothecin, digitoxin, and vinblastine in vitro. We have also established that this sensitization is reliant on the ROS response generated by gentamicin.