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.