2’-Methylklavuzon Causes Lipid-Lowering Effects on A549 Non-Small Cell Lung Cancer Cells and Significant Changes on Dna Structure Evidenced by Fourier Transform Infrared Spectroscopy

Abstract

Various chemical agents are used in the treatment of Non-Small Cell Lung Cancer (NSCLC). 2?-methylklavuzon was proposed as a potential chemotherapeutic agent in cancer treatment based on its topoisomerase inhibition activity. In this study the cellular effects of 2?-methylklavuzon was evaluated on A549 cancer cells using FTIR spectroscopy. 2?-methylklavuzon induced significant changes on both the whole cell lyophilizates and the lipid extracts of the A549 lung cancer cells. 2?-methylklavuzon caused significant structural changes in A549 cell DNA structure: T, A and G DNA breathing modes are lost after the drug application indicating the loss of topoisomerase activity. The level of transcription and RNA synthesis was enhanced. 2?-methylklavuzon induced single stranded DNA formation evidenced by the increase in the ratio of asymmetric/symmetric phosphate stretching modes. 2?-methylklavuzon induced band shifts only in the asymmetric mode of phosphate bonds not in the symmetrical phosphate bond stretching. 2?-methylklavuzon induced A form of DNA topography. In addition to the changes in the DNA structure and transcription 2?-methylklavuzon also caused lipid-lowering effect in A549 cancer cells. 2?-methylklavuzon suppressed lipid unsaturation, however, it induced formation of lipids with ring structures. 2?-methylklavuzon suppressed phosphate-containing lipids significantly and decreased carbonyl containing lipids and cholesterol slightly. 2?-methylklavuzon caused increases in the hydrocarbon chain length. Overall, 2?-methylklavuzon can be used as a lipid-lowering compound in the treatment of NSCLC and other cancer therapies. © 2020 Elsevier B.V.