Novel tetrahydroacridine derivatives inhibit human lung adenocarcinoma cell growth by inducing G1 phase cell cycle arrest and apoptosis

• Published in: Biomedicine & pharmacotherapy 2014-10, Vol.68 (8), p.959-967
• Main Authors: Olszewska, Paulina, Mikiciuk-Olasik, Elżbieta, Błaszczak-Świątkiewicz, Katarzyna, Szymański, Jacek, Szymański, Paweł
• Format: Article
• Language: English
• Subjects: Acridine derivatives; Acridines - chemistry; Acridines - pharmacology; Acridines - therapeutic use; Adenocarcinoma - drug therapy; Adenocarcinoma - pathology; Adenocarcinoma of Lung; Anticancer compounds; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Apoptosis - drug effects; Apoptosis - physiology; Cell Line, Tumor; Cell Survival - drug effects; Cell Survival - physiology; DNA intercalation; Dose-Response Relationship, Drug; G1 Phase Cell Cycle Checkpoints - drug effects; G1 Phase Cell Cycle Checkpoints - physiology; Growth Inhibitors - chemistry; Growth Inhibitors - pharmacology; Growth Inhibitors - therapeutic use; Humans; Internal Medicine; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Medical Education; Tetrahydroacridine derivatives
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2014.10.018

Abstract Lung cancer is not only the most commonly diagnosed cancers worldwide but it is still the leading cause of cancer-related death. Acridine derivatives are a class of anticancer agents with the ability to intercalate DNA and inhibit topoisomerases. The aim of this study was to evaluate the effect of sixteen new tetrahydroacridine derivatives on the viability and growth of human lung adenocarcinoma cells. We compared anticancer activity of a series of eight compounds with 4-fluorobenzoic acid and eight compounds with 6-hydrazinonicotnic acid differed from each other in length of the aliphatic chain containing from 2 to 9 carbon atoms. Interestingly, tetrahydroacridine with 4-fluorobenzoic acid (compounds 9 – 16 ) showed higher anticancer activity than derivatives with 6-hydrazinonicotnic acid (compounds 1–8 ) and their efficacy was correlated with increasing number of carbon atoms in the aliphatic chain. The results showed that inhibition of cancer cell growth by the most effective compounds 15 and 16 was associated with induction of G1 phase cell cycle arrest followed by caspase-3 dependent apoptosis. Our findings suggest that tetrahydroacridine with 4-fluorobenzoic acid containing 8 and 9 carbon atoms may be potential candidate for treatment of lung cancer.