Raman micro spectroscopy study of the interaction of vincristine with A549 cells supported by expression analysis of bcl-2 protein

Understanding the interaction of anticancer drugs with model cell lines is important to elucidate the mode of action of these drugs as well as to develop cost effective and rapid screening methods. Raman spectroscopy has been demonstrated to be a valuable technique for high throughput, noninvasive a...

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Published inAnalyst (London) Vol. 138; no. 20; pp. 6177 - 6184
Main Authors Nawaz, Haq, Garcia, Amaya, Meade, Aidan D, Lyng, Fiona M, Byrne, Hugh J
Format Journal Article
LanguageEnglish
Published England 21.10.2013
Subjects
Cell Line, Tumor
Correlation analysis
Deoxyribonucleic acid
Dose-Response Relationship, Drug
Drugs
Gene Expression Regulation, Neoplastic
Humans
Intercalation
Nuclei
Protein Binding - physiology
Proteins
Proto-Oncogene Proteins c-bcl-2 - biosynthesis
Spectra
Spectroscopy
Spectrum Analysis, Raman - methods
Vincristine - analysis
Vincristine - metabolism
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Summary:Understanding the interaction of anticancer drugs with model cell lines is important to elucidate the mode of action of these drugs as well as to develop cost effective and rapid screening methods. Raman spectroscopy has been demonstrated to be a valuable technique for high throughput, noninvasive analysis. The interaction of vincristine with a human lung adenocarcinoma cell line (A549) was investigated using Raman micro spectroscopy. The results were correlated with parallel measurements from the MTT cytotoxicity assay, which yielded an IC50 value of 0.10 ± 0.03 μM. The Raman spectral data acquired from vincristine treated A549 cells was analysed to understand its interaction with the nucleus in the cell and elucidate DNA intercalation. The dose dependent spectral changes in the nucleus are analysed by PLS-Jack knifing for the identification of the more significant changes associated with the mode of action of the drug. Results are correlated with a similar dose dependent expression analysis of the bcl-2 protein, an anti-apoptotic protein associated with DNA damage, in the vincristine treated A549 cells using flow cytometry. The results indicate the co-existence of two modes of action, microtubule binding at low doses and DNA intercalation at high doses.
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ISSN:0003-2654
1364-5528
DOI:10.1039/c3an00975k