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http://dx.doi.org/10.5352/JLS.2012.22.9.1145

Combined Treatment of Sodium Salicylate and Genistein Induces Incomplete Apoptosis and Necrosis in MCF-7 Multicellular Tumor Spheroids  

Lee, Su-Yeon (Department of Molecular Biology, College of Natural Sciences, Pusan National University)
Kim, Cho-Hee (Department of Molecular Biology, College of Natural Sciences, Pusan National University)
Jeon, Hyun-Min (Department of Molecular Biology, College of Natural Sciences, Pusan National University)
Ju, Min-Kyung (Department of Molecular Biology, College of Natural Sciences, Pusan National University)
Kim, Min-Young (Department of Molecular Biology, College of Natural Sciences, Pusan National University)
Jeong, Eui-Kyong (Department of Molecular Biology, College of Natural Sciences, Pusan National University)
Park, Hye-Gyeong (Nanobiotechnology Center, Pusan National University)
Kang, Ho-Sung (Department of Molecular Biology, College of Natural Sciences, Pusan National University)
Publication Information
Journal of Life Science / v.22, no.9, 2012 , pp. 1145-1151 More about this Journal
Abstract
Aspirin and its deacetylated form, sodium salicylate (NaSal), have been shown to exert chemopreventive activities against many human cancers including those of the colon, lung, and breast. Previously, we showed that combined treatment of NaSal and genistein synergistically induced apoptosis in A549 lung cancer cells, indicating that these two natural chemicals could be used in combination for cancer therapy. In this study, we examined effects of NaSal/genistein combined treatment on other cancer cells and in three-dimensional multicellular tumor spheroid (MTS) and in an in vitro solid tumor model. We found that the combined treatment induces apoptosis in the HCT116 cells and the A549 cells, but not in the MCF-7 cells. Interestingly, the MCF-7 cells responded to the NaSal/genistein combined treatment by undergoing cell death when they were cultivated as MTS. The combined treatment induced apoptosis at an earlier stage in the MCF-7 MTS culture. However, when the MCF-7 MTS was cultivated for a longer period, it induced necrosis rather than apoptosis. We further found that the apoptotic pattern observed in MCF-7 MTS was incomplete: the chromatins were condensed and fragmented, but the nuclear membrane was still intact. Taken together, these results demonstrate that the NaSal/genistein combined treatment induces incomplete apoptosis and necrosis in the MCF-7 MTS culture system.
Keywords
Salicylate; genistein; apoptosis; necrosis; MCF-7 multicellular tumor spheroids;
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1 Amann, R. and Peskar, B. A. 2002. Anti-inflammatory effects of aspirin and sodium salicylate. Eur. J. Pharmacol. 447, 1-9.   DOI   ScienceOn
2 Bellosillo, B., Pique, M., Barragan, M., Castano, E., Villamor, N., Colomer, D., Montserrat, E., Pons, G. and Gil, J. 1998. Aspirin and salicylate induce apoptosis and activation of caspases in B-cell chronic lymphocytic leukemia cells. Blood 92, 1406-1414.
3 Dikshit, P., Chatterjee, M., Goswami, A., Mishra, A. and Jana, N. R. 2006. Aspirin induces apoptosis through the inhibition of proteasome function. J. Biol. Chem. 281, 29228-29235.   DOI   ScienceOn
4 Dixon, R. A. and Ferreira, D. 2002. Genistein. Phytochemistry 60, 205-211.   DOI   ScienceOn
5 Flossmann, E. and Rothwell, P. M. 2007. Effect of aspirin on long-term risk of colorectal cancer: consistent evidence from randomised and observational studies. Lancet 369, 1603-1613.   DOI
6 Garg, A. K., Buchholz, T. A. and Aggarwal, B. B. 2005. Chemosensitization and radiosensitization of tumors by plant polyphenols. Antioxid. Redox Signal. 7, 1630-1647.   DOI
7 Golstein, P. and Kroemer, G. 2007. Cell death by necrosis: towards a molecular definition. Trends Biochem. Sci. 32, 37-43.   DOI
8 Horning, J. L., Sahoo, S. K., Vijayaraghavalu, S., Dimitrijevic, S., Vasir, J. K., Jain, T. K., Panda, A. K. and Labhasetwar, V. 2008. 3-D tumor model for in vitro evaluation of anticancer drugs. Mol. Pharm. 5, 849-862.   DOI
9 Ivascu, A. and Kubbies, M. 2007. Diversity of cell-mediated adhesions in breast cancer spheroids. Int. J. Oncol. 31, 1403-1413.
10 Jeong, E. K., Lee, S. Y., Jeon, H. M., Ju, M. K., Kim, C. H. and Kang, H. S. 2010. Role of extracellular signal-regulated kinase (ERK)1/2 in multicellular resistance to docetaxel in MCF-7 cells. Int. J. Oncol. 37, 655-661.
11 Kim, C. H., Jeon, H. M., Lee, S. Y., Ju, M. K., Moon, J. Y., Park, H. G., Yoo, M. A., Choi, B. T., Yook, J. I., Lim, S. C., Han, S. I. and Kang, H. S. 2011. Implication of snail in metabolic stress-induced necrosis. PLoS One 6, e18000.   DOI
12 Kim, C. H., Kim, M. Y., Moon, J. Y., Hwang, J. W., Lee, S. Y., Joo, Y. M., Han, S. I., Park, H. G. and Kang, H. S. 2008. Implication of NAG-1 in synergistic induction of apoptosis by combined treatment of sodium salicylate and PI3K/MEK1/2 inhibitors in A549 human lung adenocarcinoma cells. Biochem. Pharmacol. 75, 1751-1760.   DOI
13 Klampfer, L., Cammenga, J., Wisniewski, H. G. and Nimer, S. D. 1999. Sodium salicylate activates caspases and induces apoptosis of myeloid leukemia cell lines. Blood 93, 2386-2394.
14 Law, B. K., Waltner-Law, M. E., Entingh, A. J., Chytil, A., Aakre, M. E., Norgaard, P. and Moses, H. L. 2000. Salicylate-induced growth arrest is associated with inhibition of p70s6k and down-regulation of c-myc, cyclin D1, cyclin A, and proliferating cell nuclear antigen. J. Biol. Chem. 275, 38261-38267.   DOI
15 Lee, E. J., Park, H. G. and Kang, H. S. 2003. Sodium salicylate induces apoptosis in HCT116 colorectal cancer cells through activation of p38MAPK. Int. J. Oncol. 23, 503-508.
16 Ruchaud, S., Korfali, N., Villa, P., Kottke, T. J., Dingwall, C., Kaufmann, S. H. and Earnshaw, W. C. 2002. Caspase-6 gene disruption reveals a requirement for lamin A cleavage in apoptotic chromatin condensation. Embo J. 21, 1967-1977.   DOI   ScienceOn
17 Lee, S. Y., Jeong, E. K., Jeon, H. M., Ju, M. K., Kim, C. H., Park, H. G. and Kang, H. S. 2011. HMGB1 Switches Alkylating DNA Damage-Induced Apoptosis to Necrosis. J. Life Sci. 21, 953-960.   DOI
18 Lotze, M. T. and Tracey, K. J. 2005. High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal. Nat. Rev. Immunol. 5, 331-342.   DOI
19 Marra, D. E., Simoncini, T. and Liao, J. K. 2000. Inhibition of vascular smooth muscle cell proliferation by sodium salicylate mediated by upregulation of p21(Waf1) and p27(Kip1). Circulation 102, 2124-2130.   DOI
20 Scaffidi, P., Misteli, T. and Bianchi, M. E. 2002. Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature 418, 191-195.   DOI   ScienceOn
21 Tomes, L., Emberley, E., Niu, Y., Troup, S., Pastorek, J., Strange, K., Harris, A. and Watson, P. H. 2003. Necrosis and hypoxia in invasive breast carcinoma. Breast Cancer Res. Treat. 81, 61-69.   DOI
22 Ulrich, C. M., Bigler, J. and Potter, J. D. 2006. Non-steroidal anti-inflammatory drugs for cancer prevention: promise, perils and pharmacogenetics. Nat. Rev. Cancer 6, 130-140.   DOI
23 Vakkila, J. and Lotze, M. T. 2004. Inflammation and necrosis promote tumour growth. Nat. Rev. Immunol. 4, 641-648.   DOI
24 Yeh, T. C., Chiang, P. C., Li, T. K., Hsu, J. L., Lin, C. J., Wang, S. W., Peng, C. Y. and Guh, J. H. 2007. Genistein induces apoptosis in human hepatocellular carcinomas via interaction of endoplasmic reticulum stress and mitochondrial insult. Biochem. Pharmacol. 73, 782-792.   DOI
25 Zong, W. X. and Thompson, C. B. 2006. Necrotic death as a cell fate. Genes Dev. 20, 1-15.   DOI