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


Ceylan C., Aksoy H. N., Cagir A., Çetinkaya H.

Vibrational Spectroscopy, cilt.111, 2020 (SCI-Expanded, Scopus)

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 111
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1016/j.vibspec.2020.103148
  • Dergi Adı: Vibrational Spectroscopy
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aerospace Database, Analytical Abstracts, Chemical Abstracts Core, Chimica, Communication Abstracts, Compendex, INSPEC, Metadex, Civil Engineering Abstracts
  • Anahtar Kelimeler: 2’-methylklavuzon, A549 cells, CRM1 inhibitor, Fourier transform infrared (FTIR), Non-Small cell lung cancer (NSCLC), Topoisomerase 1 inhibitor
  • Hacettepe Üniversitesi Adresli: Evet

Özet

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.