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The TSPO Ligands MGV-1 and 2-Cl-MGV-1 Differentially Inhibit the Cigarette Smoke-Induced Cytotoxicity to H1299 Lung
Nidal Zeineh1, Rafael M Nagler1, Martin Gabay1
1Department of Neuroscience, The Ruth and Bruce Rappaport Faculty of Medicine, Technion Institute of Technology, Haifa 31096, Israel.
Abstract:
TSPO is involved in cigarette smoke (CS)-induced cellular toxicity, which may result in oral and pulmonary diseases and lung cancer. H1299 lung cancer cells were exposed directly to CS. The H1299 cells were pretreated with our TSPO ligands MGV-1 and 2-Cl-MGV-1 (Ki = 825 nM for both) at a concentration of 25 µM 24 h prior to CS exposure. Cell death and apoptotic markers were measured, in addition to TSPO expression levels, ATP synthase activity, generation of reactive oxygen species (ROS), depolarization of mitochondrial membrane potential (ΔΨm), cAMP and LDH levels. Pretreatment with MGV-1 and 2-Cl-MGV-1 (25 µM), 24 h prior to CS exposure, differentially attenuated the CS-induced cellular insult as well as cell death in H1299 lung cancer cells. These protective effects included prevention of ATP synthase reversal, ROS generation, depolarization of the mitochondrial membrane and elevation in LDH. The preventive efficacy of 2-Cl-MGV-1 was superior to that achieved by MGV-1. Both ligands did not prevent the elevation in cAMP. These findings may indicate a mild protective effect of these TSPO ligands in CS-related pulmonary and keratinocyte cellular pathology.
Insights
TSPO ligands MGV-1 and 2-Cl-MGV-1 offer mild protection against cigarette smoke (CS) cellular damage in lung cancer cells. 2-Cl-MGV-1 demonstrated superior efficacy in preventing CS-induced cell death and toxicity.
Area of Science:
- Biochemistry
- Cell Biology
- Toxicology
Background:
- Cigarette smoke (CS) induces cellular toxicity, contributing to oral, pulmonary diseases, and lung cancer.
- Translocator Protein (TSPO) is implicated in CS-induced cellular damage.
Purpose of the Study:
- To investigate the protective effects of novel TSPO ligands, MGV-1 and 2-Cl-MGV-1, against CS-induced cellular toxicity in H1299 lung cancer cells.
- To evaluate the impact of these ligands on various cellular damage markers.
Main Methods:
- H1299 lung cancer cells were pretreated with TSPO ligands (MGV-1, 2-Cl-MGV-1) 24 hours before direct exposure to CS.
- Assessed cell death, apoptotic markers, TSPO expression, ATP synthase activity, reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), cAMP, and lactate dehydrogenase (LDH) levels.
Main Results:
- Both ligands attenuated CS-induced cellular insult and cell death.
- Protective effects included preventing ATP synthase reversal, ROS generation, mitochondrial membrane depolarization, and LDH elevation.
- 2-Cl-MGV-1 exhibited superior protective efficacy compared to MGV-1.
- Neither ligand prevented the elevation of cAMP levels.
Conclusions:
- TSPO ligands MGV-1 and 2-Cl-MGV-1 show potential for mild protective effects against CS-related cellular pathology.
- The findings suggest a role for TSPO modulation in mitigating CS-induced lung damage.
