Tin Mesoporphyrin Selectively Reduces Non-Small-Cell Lung Cancer Cell Line A549 Proliferation by Interfering with Heme Oxygenase and Glutathione Systems

• Published in: Biomolecules (Basel, Switzerland) Vol. 11; no. 6; p. 917
• Main Authors: Sorrenti, Valeria, D’Amico, Agata Grazia, Barbagallo, Ignazio, Consoli, Valeria, Grosso, Salvo, Vanella, Luca
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 21.06.2021; MDPI
• Subjects: Antibodies; Antioxidants; Antitumor agents; Apoptosis; cancer; Carbon monoxide; Cell growth; Cell migration; Cell proliferation; Chemoresistance; Chemotherapy; Communication; Dehydrogenases; Enzymes; Gene expression; Glucose; Glucosephosphate dehydrogenase; Glutathione; Glycolysis; Heme; Heme oxygenase (decyclizing); heme-oxygenase; Homeostasis; Hyperbilirubinemia; Infrared imaging systems; Lung cancer; Metabolism; Neonates; Non-small cell lung carcinoma; Oxidative stress; Oxygenase; p53 Protein; Pentose phosphate pathway; porphyrins; Proteins; Reactive oxygen species; Small cell lung carcinoma; Tin; Tumorigenesis; United States > US; Italy
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom11060917

In order to maintain redox homeostasis, non-small-cell lung cancer (NSCLC) increases the activation of many antioxidant systems, including the heme-oxygenase (HO) system. The overexpression of HO-1 has been often associated with chemoresistance and tumor aggressiveness. Our results clearly showed an overexpression of the HO-1 protein in A549 NSCLC cell lines compared to that in non-cancerous cells. Thus, we hypothesized that “off-label” use of tin mesoporphyrin, a well-known HO activity inhibitor clinically used for neonatal hyperbilirubinemia, has potential use as an anti-cancer agent. The pharmacological inhibition of HO activity caused a reduction in cell proliferation and migration of A549. SnMP treatment caused an increase in oxidative stress, as demonstrated by the upregulation of reactive oxygen species (ROS) and the depletion of glutathione (GSH) content. To support these data, Western blot analysis was performed to analyze glucose-6-phosphate dehydrogenase (G6PD), TP53-induced glycolysis and the apoptosis regulator (TIGAR), and the glutamate cysteine ligase catalytic (GCLC) subunit, as they represent the main regulators of the pentose phosphate pathway (PPP) and glutathione synthesis, respectively. NCI-H292, a subtype of the NSCLC cell line, did not respond to SnMP treatment, possibly due to low basal levels of HO-1, suggesting a cellular-dependent antitumorigenic effect. Altogether, our results suggest HO activity inhibition may represent a potential target for selective chemotherapy in lung cancer subtypes.