Increased unsaturation of lipids in cytoplasmic lipid droplets in DAOY cancer cells in response to cisplatin treatment
Increases in 1H nuclear magnetic resonance spectroscopy (NMR) visible lipids are a well-documented sign of treatment response in cancers. Lipids in cytoplasmic lipid droplets (LDs) are the main contributors to the NMR lipid signals. Two human primitive neuroectodermal tumour cell lines with different sensitivities to cisplatin treatment were studied. Increases in NMR visible saturated and unsaturated lipids in cisplatin treated DAOY cells were associated with the accumulation of LDs prior to DNA fragmentation due to apoptosis. An increase in unsaturated fatty acids (UFAs) was detected in isolated LDs from DAOY cells, in contrast to a slight decrease in UFAs in lipid extracts from whole cells. Oleic acid and linoleic acid were identified as the accumulating UFAs in LDs by heteronuclear single quantum coherence spectroscopy (HSQC). 1H NMR lipids in non-responding PFSK-1 cells were unchanged by exposure to 10 μM cisplatin. These findings support the potential of NMR detectable UFAs to serve as a non-invasive marker of tumour cell response to treatment.
- Bakshi, A., Mukherjee, D., Bakshi, A., Banerji, A. K., & Das, U. N. (2003). γ-Linolenic acid therapy of human gliomas. Nutrition, 19, 305–309. doi:10.1016/s0899-9007(02)00862-6. CrossRef
- Bayet-Robert, M., et al. (2010). Quantitative two-dimensional HRMAS 1H-NMR spectroscopy-based metabolite profiling of human cancer cell lines and response to chemotherapy. Magnetic Resonance in Medicine, 63, 1172–1183. doi:10.1002/mrm.22303. CrossRef
- Boren, J., & Brindle, K. M. (2012). Apoptosis-induced mitochondrial dysfunction causes cytoplasmic lipid droplet formation. Cell Death and Differentiation,. doi:10.1038/cdd.2012.34.
- Burns, C. P., & Spector, A. A. (1994). Biochemical effects of lipids on cancer therapy. The Journal of Nutritional Biochemistry, 5, 114–123. CrossRef
- Cockbain, A. J., Toogood, G. J., & Hull, M. A. (2012). Omega-3 polyunsaturated fatty acids for the treatment and prevention of colorectal cancer. Gut, 61, 135–149. doi:10.1136/gut.2010.233718. CrossRef
- Delikatny, E. J., Cooper, W. A., Brammah, S., Sathasivam, N., & Rideout, D. C. (2002). Nuclear magnetic resonance-visible lipids induced by cationic lipophilic chemotherapeutic agents are accompanied by increased lipid droplet formation and damaged mitochondria. Cancer Research, 62, 1394–1400.
- Griffin, J. L., et al. (2003). Assignment of 1H nuclear magnetic resonance visible polyunsaturated fatty acids in BT4C gliomas undergoing ganciclovir-thymidine kinase gene therapy-induced programmed cell death. Cancer Research, 63, 3195–3201.
- Hakumaki, J. M., Poptani, H., Sandmair, A. M., Yla-Herttuala, S., & Kauppinen, R. A. (1999). 1H MRS detects polyunsaturated fatty acid accumulation during gene therapy of glioma: Implications for the in vivo detection of apoptosis. Nature Medicine, 5, 1323–1327. doi:10.1038/15279. CrossRef
- Herber, D. L., et al. (2010). Lipid accumulation and dendritic cell dysfunction in cancer. Nature Medicine, 16, 880–886. CrossRef
- Jakacki, R. I., et al. (2012). Outcome of children with metastatic medulloblastoma treated with carboplatin during craniospinal radiotherapy: A children’s oncology group phase I/II study. Journal of Clinical Oncology. doi:10.1200/JCO.2011.40.2792.
- Kim, H. J., et al. (2012). Phase II study of palliative S-1 in combination with cisplatin as second-line chemotherapy for gemcitabine-refractory pancreatic cancer patients. Oncology Letters, 3, 1314–1318. doi:10.3892/ol.2012.637.
- Mirbahai, L., et al. (2012). Lipid biomarkers of glioma cell growth arrest and cell death detected by 1H magic angle spinning MRS. NMR in Biomedicine. doi:10.1002/nbm.2796.
- Musacchio, T., Toniutti, M., Kautz, R., & Torchilin, V. P. (2009). 1H NMR detection of mobile lipids as a marker for apoptosis: The case of anticancer drug-loaded liposomes and polymeric micelles. Molecular Pharmaceutics, 6, 1876–1882. doi:10.1021/mp900164n. CrossRef
- Opstad, K. S., Bell, B. A., Griffiths, J. R., & Howe, F. A. (2008). An investigation of human brain tumour lipids by high-resolution magic angle spinning 1H MRS and histological analysis. NMR in Biomedicine, 21, 677–685. CrossRef
- Pan, X., et al. (2012). The lipid composition of isolated cytoplasmic lipid droplets from a human cancer cell line, BE(2)M17. Molecular BioSystems, 8, 1694–1700. doi:10.1039/C2MB05485J. CrossRef
- Quintero, M., Cabanas, M. E., & Arus, C. (2007). A possible cellular explanation for the NMR-visible mobile lipid (ML) changes in cultured C6 glioma cells with growth. BBA-Biochimica et Biophysica Acta, 1771, 31–44. CrossRef
- Scheim, D. E. (2009). Cytotoxicity of unsaturated fatty acids in fresh human tumor explants: Concentration thresholds and implications for clinical efficacy. Lipids in Health and Disease, 8, 54. CrossRef
- Schmitz, J. E., Kettunen, M. I., Hu, D. E., & Brindle, K. M. (2005). 1H MRS-visible lipids accumulate during apoptosis of lymphoma cells in vitro and in vivo. Magnetic Resonance in Medicine, 54, 43–50. CrossRef
- Shih, C. M., et al. (2005). Detection of apoptosis and necrosis in normal human lung cells using 1H NMR spectroscopy. Annals of the New York Academy of Sciences, 1042, 488–496. doi:10.1196/annals.1338.042. CrossRef
- Shulman, K., Haim, N., Wollner, M., Bernstein, Z., Abdah-Bortnyak, R., & Bar-Sela, G. (2012). Postoperative chemotherapy in gastric cancer, consisting of etoposide, doxorubicin and cisplatin, followed by radiotherapy with concomitant cisplatin: A feasibility study. Oncology Letters, 3, 1154–1158. doi:10.3892/ol.2012.617.
- Tanida, S., et al. (2012). Mechanisms of cisplatin-induced apoptosis and of cisplatin sensitivity: Potential of BIN1 to act as a potent predictor of cisplatin sensitivity in gastric cancer treatment. International Journal of Surgical Oncology, 2012, 862879. doi:10.1155/2012/862879. CrossRef
- Weller, P. F., Ryeom, S. W., Picard, S. T., Ackerman, S. J., & Dvorak, A. M. (1991). Cytoplasmic lipid bodies of neutrophils: formation induced by cis-unsaturated fatty acids and mediated by protein kinase C. Journal of Cell Biology, 113, 137–146. CrossRef
- Xi, Y., & Rocke, D. M. (2008). Baseline correction for NMR spectroscopic metabolomics data analysis. BMC Bioinformatics, 9, 324. CrossRef
- Zietkowski, D., Payne, G. S., Nagy, E., Mobberley, M. A., Ryder, T. A., & Desouza, N. M. (2012). Comparison of NMR lipid profiles in mitotic arrest and apoptosis as indicators of paclitaxel resistance in cervical cell lines. Magnetic Resonance in Medicine, 68, 369–377. doi:10.1002/mrm.23265. CrossRef
- Increased unsaturation of lipids in cytoplasmic lipid droplets in DAOY cancer cells in response to cisplatin treatment
- Open Access
- Available under Open Access This content is freely available online to anyone, anywhere at any time.
Volume 9, Issue 3 , pp 722-729
- Cover Date
- Print ISSN
- Online ISSN
- Springer US
- Additional Links
- Lipid droplets
- 1H NMR
- Industry Sectors
- Author Affiliations
- 1. Cancer Sciences, University of Birmingham, Birmingham, NH, UK
- 2. Birmingham Children’s Hospital NHS Foundation Trust, Birmingham, NH, UK
- 3. Electronic, Electrical and Computer Engineering, University of Birmingham, Birmingham, NH, UK
- 4. Department of Biochemistry and the Cambridge Systems Biology Centre, University of Cambridge, Cambridge, NH, UK
- 5. Clinical Research and Imaging Centre and Department of Experimental Psychology, University of Bristol, Bristol, NH, UK
- 6. Institute of Child Health, Whittall Street, Birmingham, B4 6NH, NH, UK