engleski

Attenuated Total Reflectance - Fourier Transform Infrared spectroscopy (ATR-FTIR) reveales increased cholesterol esters in drug resistant laryngeal carcinoma cells

The major obstacle to the successful chemotherapy in the clinical management of human cancers is drug resistance. Cellular, molecular, and physiological investigation of the mechanisms underlying drug resistance has identified multiple factors involved in this phenomenon. Unlike conventional techniques used in cellular or molecular biology, infrared spectroscopy is developing as new and more holistic approach to studying drug resistance. It yields a unique fingerprint of all molecules present in the cell (proteins, lipids, nucleic acids and other chemical species present) and gives information about their nature and quantities. In our laboratory we have developed carboplatin resistant subline 7T from human laryngeal carcinoma HEp-2 cells. In our previous work we have explored the anticancer potential of natural compound curcumin on HEp-2 and 7T cells. Although few literature data suggest that curcumin may revert drug resistance of cancer cells, we reported for the first time that drug resistant cells may be also cross resistant to curcumin, and we investigated some of the possible mechanisms involved in this phenomenon. In order to shed more light on the molecular mechanism of curcumin resistance in 7T cells, we used FTIR-ATR spectroscopy. By comparing the spectra from parental HEp-2 and resistant 7T subline, we found that the most interesting difference was the increase in cholesterol ester content recorded in resistant 7T cells. According to the literature, cholesterol esters are localized in lipid droplets. It is now well established that these structures are highly regulated organelles involved in many aspects of cell activation and metabolism, inflammatory and neoplastic processes, and therefore they could be the potential targets for novel antineoplastic therapies. We confirmed existence of lipid droplets and their serum dependence in resistant 7T cells, but almost none of these properties were found in HEp-2 cells. Our results clearly show the usefulness of FTIR-ATR spectroscopy as a new technique in cellular or molecular biology research.

drug resistance; FTIR-ATR spectroscopy; cholesterol esters

Rad je prezentiran i na skupu 2nd Meeting of the Croatian Association for Cancer Research with International Participation, održanom od 08.-09.11.2012.g., Zagreb, Hrvatska ; Knjiga sažetaka obajvljena u Periodicum biologorum 114 (2012) (S1) str. 70-70.