The TSPO Ligands MGV-1 and 2-Cl-MGV-1 Differentially Inhibit the Cigarette Smoke-Induced Cytotoxicity to H1299 Lung Cancer Cells
by
and
Nidal Zeineh
1, 
Rafael M. Nagler
1,
Martin Gabay
1,
Fadi Obeid
1,
Meygal Kahana
1,
Abraham Weizman
2,3
and
Moshe Gavish
1,* 1
Department of Neuroscience, The Ruth and Bruce Rappaport Faculty of Medicine, Technion Institute of Technology, Haifa 31096, Israel
2
Research Unit, Geha Mental Health Center and Laboratory of Biological Psychiatry, Felsenstein Medical Research Center, Petah Tikva 4910002, Israel
3
Departments of Psychiatry, Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
*
Author to whom correspondence should be addressed.
Biology 2021, 10(5), 395; https://doi.org/10.3390/biology10050395
Submission received: 2 March 2021
/
Revised: 17 April 2021
/
Accepted: 29 April 2021
/
Published: 2 May 2021
(This article belongs to the Special Issue TSPO in the Pathways of Neuroinflammation and Apoptosis)
Simple Summary
In this study, we investigated the impact of CS on various TSPO-related mitochondrial processes, and the protective ability of our novel TSPO ligands against such CS-induced cellular damages. Our results support the previously reported role of TSPO in apoptotic cell death. Moreover, the present data demonstrate the protective effect of our TSPO ligands against CS-induced cellular damage.
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.
