Comparison of Metabolic Profiles of Normal and Cancer Cells in Response to Cytotoxic Agents
0
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Together with radiotherapy, chemotherapy using cytotoxic agents is one of the most common therapies in cancer. Metabolic changes in cancer cells are drawing much attention recently, but the metabolic alterations by anticancer agents have not been much studied. Here, we investigated the effects of commonly used cytotoxic agents on lung normal cell MRC5 and lung cancer cell A549. We employed cis-plastin, doxorubicin, and 5-Fluorouracil and compared their effects on the viability and metabolism of the normal and cancer cell lines. We first established the concentration of the cytotoxic reagents that give differences in the viabilities of normal and cancer cell lines. In those conditions, the viability of A549 decreased significantly, whereas that of MRC5 remained unchanged. To study the metabolic alterations implicated in the viability differences, we obtained the metabolic profiles using 1H-NMR spectrometry. The 1H-NMR data showed that the metabolic changes of A549 cells are more remarkable than that of MRC5 cells and the effect of 5-FU on the A549 cells is the most distinct compared to other treatments. Heat map analysis showed that metabolic alterations under treatment of cytotoxic agents are totally different between normal and cancer cells. Multivariate analysis and weighted correlation network analysis (WGCNA) revealed a distinctive metabolite signature and hub metabolites. Two different analysis tools revealed that the changes of cell metabolism in response to cytotoxic agents were highly correlated with the Warburg effect and Reductive lipogenesis, two pathways having important effects on the cell survival. Taken together, our study addressed the correlation between the viability and metabolic profiles of MRC5 and A549 cells upon the treatment of cytotoxic anticancer agents.
Abstract
Together with radiotherapy, chemotherapy using cytotoxic agents is one of the most common therapies in cancer. Metabolic changes in cancer cells are drawing much attention recently, but the metabolic alterations by anticancer agents have not been much studied. Here, we investigated the effects of commonly used cytotoxic agents on lung normal cell MRC5 and lung cancer cell A549. We employed cis-plastin, doxorubicin, and 5-Fluorouracil and compared their effects on the viability and metabolism of the normal and cancer cell lines. We first established the concentration of the cytotoxic reagents that give differences in the viabilities of normal and cancer cell lines. In those conditions, the viability of A549 decreased significantly, whereas that of MRC5 remained unchanged. To study the metabolic alterations implicated in the viability differences, we obtained the metabolic profiles using 1H-NMR spectrometry. The 1H-NMR data showed that the metabolic changes of A549 cells are more remarkable than that of MRC5 cells and the effect of 5-FU on the A549 cells is the most distinct compared to other treatments. Heat map analysis showed that metabolic alterations under treatment of cytotoxic agents are totally different between normal and cancer cells. Multivariate analysis and weighted correlation network analysis (WGCNA) revealed a distinctive metabolite signature and hub metabolites. Two different analysis tools revealed that the changes of cell metabolism in response to cytotoxic agents were highly correlated with the Warburg effect and Reductive lipogenesis, two pathways having important effects on the cell survival. Taken together, our study addressed the correlation between the viability and metabolic profiles of MRC5 and A549 cells upon the treatment of cytotoxic anticancer agents.
참고문헌 (44)
- P. Hammel, , Target Oncol, 7, pp.169~ (2012)
- I. F. Duarte, , Mol. pharmaceutics, 10, pp.4242~ (2013)
- M. S. Ham, , Mol. Clin. Oncol, 1, pp.373~ (2013)
- S. Lv, , Biomaterials, 35, pp.6118~ (2014)
- Z. H. Siddik, , Oncogene, 22, pp.7265~ (2003)
- A. Schulze, , Nature, 491, pp.364~ (2012)
- R. Possemato, , Nature, 476, pp.346~ (2011)
- C. M. Metallo, , Nature, 481, pp.380~ (2012)
- A. S. Lee, , Nature reviews. Cancer, 14, pp.263~ (2014)
- M. Jain, , Science, 336, pp.1040~ (2012)
- M. G. Vander Heiden, , Science, 324, pp.1029~ (2009)
- S. Akakura, , Biochem. Biophys. Res. Commun, 448, pp.461~ (2014)
- L. M. Phan, , Cancer Biol. Med, 11, pp.1~ (2014)
- R. J. DeBerardinis, , Proc. Natl. Acad. Sci. U. S. A, 104, pp.19345~ (2007)
- D. R. Wise, , Proc. Natl. Acad. Sci. U. S. A, 105, pp.18782~ (2008)
- D. I. Benjamin, , Proc. Natl. Acad. Sci. U. S. A, 110, pp.14912~ (2013)
- C. Zhu, , Sci. Rep, 4, pp.5029~ (2014)
- P. Tripathi, , J. Proteome Res, 12, pp.3519~ (2013)
- A. Irfan, , Toxicol Sci, 138, pp.354~ (2014)
- K. Akira, , J. Pharm. Biomed. Anal, 85, pp.155~ (2013)
- 윤다혜, "Investigation of Germicide and Growth Enhancer Effects on Bean Sprout using NMR-based Metabolomics", Journal of the Korean Magnetic Resonance Society, 20(4), pp.121~128 (2016), 한국자기공명학회
- 이석근, "The Role of NMR in the Field of Quantitative Analysis", Journal of the Korean Magnetic Resonance Society, 20(3), pp.87~94 (2016), 한국자기공명학회[DOI]
- J. Kim, , FEBS Lett, 581, pp.3795~ (2007)
- B. Chaneton, , Nature, 491, pp.458~ (2012)
- Jinho Kang, "NMR-Based Metabolomics Approach for the Differentiation of Ginseng (Panax ginseng) Roots from Different Origins", Archives of Pharmacal Research, 31(3), pp.330~336 (2008), 대한약학회
- H. Wen, , Phytochem. Anal, 21, pp.73~ (2010)
- P. Langfelder, , BMC Bioinf, 9, pp.559~ (2008)
- J. Wang, , J. Proteome Res, 12, pp.5302~ (2013)
- S. E. Elf, , Cancer, 120, pp.774~ (2014)
- A. L. Simons, , Cancer Res, 67, pp.3364~ (2007)
- S. Liu, , Environ. Toxicol. Pharmacol, 37, pp.150~ (2014)
- A. Lodi, , PloS one, 6, pp.e26155~ (2011)
- M. W. Dewhirst, , Radiother. Oncol, 83, pp.249~ (2007)
- Y. Zhao, , Cell Death Dis, 4, pp.e532~ (2013)
- H. J. Jang, , J. Recept. Signal Transduction Res, 33, pp.387~ (2013)
- C. Gorrini, , Nat. Rev. Drug Discovery, 12, pp.931~ (2013)
- D. T. Vincent, , Cancer Chemother. Pharmacol, 72, pp.1157~ (2013)
- S. Crawford, , Ther. Adv. Med. Oncol, 6, pp.52~ (2014)
- K. Gaurav, , Indian J. Med. Paediatr. Oncol, 33, pp.13~ (2012)
- M. B. Braga-Neto, , Dig. Dis. Sci, 53, pp.2687~ (2008)
- C. B. Newgard, , Cell Metab, 15, pp.606~ (2012)
- J. H. Cha, , PloS one, 8, pp.e77899~ (2013)
- J. Fan, , Nature, 510, pp.298~ (2014)
- J. H. Lim, , Cancer Res, 74, pp.3535~ (2014)