Browse > Article
http://dx.doi.org/10.5352/JLS.2011.21.8.1109

Apoptosis Induction by Methanol Extract of Prunus mume Fruits in Human Leukemia U937 Cells  

Chung, You-Jeong (Department of Biochemistry, Research Institute of Oriental Medicine, Dongeui University College of Oriental Medicine)
Park, Cheol (Department of Biochemistry, Research Institute of Oriental Medicine, Dongeui University College of Oriental Medicine)
Jeong, Yong-Kee (Department of Medical Bioscience, Graduate School and Department of Biotechnology, College of Natural Resources and Life Science, Dong-A University)
Choi, Yung-Hyun (Department of Biochemistry, Research Institute of Oriental Medicine, Dongeui University College of Oriental Medicine)
Publication Information
Journal of Life Science / v.21, no.8, 2011 , pp. 1109-1119 More about this Journal
Abstract
In the present study, the pro-apoptotic effects of methanol extract of Prunus mume fruits (MEPM) in human leukemia U937 cells were investigated. It was found that exposure to MEPM resulted in growth inhibition in a concentration-dependent manner by inducing apoptosis. The induction of apoptotic cell death in U937 cells by MEPM was correlated with a down-regulation of inhibitor of apoptosis protein (IAP) family, such as X-linked inhibitor of apoptosis protein (XIAP) and survivin, anti-apoptotic Bcl-2, up-regulation of FasL and cleavage of Bid. MEPM treatment also induced the proteolytic activation of caspase-3, caspase-8 and caspase-9, and degradation of caspase-3 substrate proteins, such as poly (ADP-ribose) polymerase (PARP) and ${\beta}$-catenin. In addition, apoptotic cell death induced by MEPM was significantly inhibited by z-DEVD-fmk, a caspase-3 specific inhibitor, which demonstrates the important role of caspase-3 in the apoptotic process by MEPM in U937 cells. Taken together, these findings suggest that P. mume extracts may be a potential chemotherapeutic agent for the control of human leukemia cells and further studies will be needed to identify the active compounds.
Keywords
Prunus mume; U937; apoptosis; caspase-3;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Scaffidi, C., S. Fulda, A. Srinivasan, C. Friesen, F. Li, K. J. Tomaselli, K. M. Debatin, P. H. Krammer, and M. E. Peter. 1998. Two CD95 (APO-1/Fas) signaling pathways. EMBO J. 17, 1675-1687.   DOI
2 Shi, Y. 2002. Mechanisms of caspase activation and inhibition during apoptosis. Mol. Cell 9, 459-470.   DOI
3 Shtilbans, V., M. Wu, and D. E. Burstein. 2010. Evaluation of apoptosis in cytologic specimens. Diagn. Cytopathol. 38, 685-697.   DOI
4 Slee, E. A., M. T. Harte, R. M. Kluck, B. B. Wolf, C. A. Casiano, D. D. Newmeyer, H. G. Wang, J. C. Reed, D. W. Nicholson, E. S. Alnemri, D. R. Green, and S. J. Martin. 1999. Ordering the cytochrome c-initiated caspase cascade: hierarchical activation of caspases-2, -3, -6, -7, -8, and -10 in a caspase-9-dependent manner. J. Cell Biol. 144, 281-292.   DOI
5 Li, P., D. Nijhawan, I. Budihardjo, S. M. Srinivasula, M. Ahmad, E. S. Alnemri, and X. Wang. 1997. Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 91, 479-489.   DOI
6 Liu, X., C. N. Kim, J. Yang, R. Jemmerson, and X. Wang. 1996. Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell 86, 147-157.   DOI
7 Loeb, L. A., K. R. Loeb, and J. P. Anderson JP. 2003. Multiple mutations and cancer. Proc. Natl. Acad. Sci. USA 100, 776-781.   DOI
8 Lu, B., X. Wu, Y. Dong, J. Gong, and Y. Zhang. 2009. Mutagenicity and safety evaluation of ethanolic extract of Prunus mume. J. Food Sci. 74, T82-88.   DOI
9 Luo, X., I. Budihardjo, H. Zou, C. Slaughter, and X. Wang. 1998. Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Cell 94, 481-490.   DOI
10 Meiler, J., and M. Schuler. 2006. Therapeutic targeting of apoptotic pathways in cancer. Curr. Drug. Targets 7, 1361-1369.   DOI
11 Miyazawa, M., H. Utsunomiya, K. Inada, T. Yamada, Y. Okuno, H. Tanaka, and M. Tatematsu. 2006. Inhibition of Helicobacter pylori motility by (+)-Syringaresinol from unripe Japanese apricot. Biol. Pharm. Bull. 29, 172-173.   DOI
12 Mori, S., T. Sawada, T. Okada, T. Ohsawa, M. Adachi, and K. Keiichi. 2007. New anti-proliferative agent, MK615, from Japanese apricot "Prunus mume" induces striking autophagy in colon cancer cells in vitro. World J. Gastroenterol. 13, 6512-6517.   DOI
13 Nakagawa, A., T. Sawada, T. Okada, T. Ohsawa, M. Adachi, and K. Kubota. 2007. New antineoplastic agent, MK615, from UME (a Variety of) Japanese apricot inhibits growth of breast cancer cells in vitro. Breast J. 13, 44-49.   DOI
14 Han, S. I., Y. S. Kim, and T. H. Kim. 2008. Role of apoptotic and necrotic cell death under physiologic conditions. BMB Rep. 41, 1-10.   DOI
15 Harris, M. H. and C. B. Thompson. 2000. The role of the Bcl-2 family in the regulation of outer mitochondrial membrane permeability. Cell Death Differ. 7, 1182-1191.   DOI
16 Jin, Z. and W. S. El-Deiry. 2005. Overview of cell death signaling pathways. Cancer Biol. Ther. 4, 139-163.   DOI
17 Kekre, N., C. Griffin, J. McNulty, and S. Pandey. 2005. Pancratistatin causes early activation of caspase-3 and the flipping of phosphatidyl serine followed by rapid apoptosis specifically in human lymphoma cells. Cancer Chemother. Pharmacol. 56, 29-38.   DOI
18 Khan, N., V. M. Adhami, and H. Mukhtar. 2008. Apoptosis by dietary agents for prevention and treatment of cancer. Biochem. Pharmacol. 76, 1333-1339.   DOI
19 Korsmeyer, S. J. 1999. BCL-2 gene family and the regulation of programmed cell death. Cancer Res. 59, 1693s-1700s.
20 Kim, B. J., J. H. Kim, H. P. Kim, and M. Y. Heo. 1997. Biological screening of 100 plant extracts for cosmetic use (II): anti-oxidative activity and free radical scavenging activity. Int. J. Cosmet. Sci. 19, 299-307.   DOI
21 Kroemer, G. and J. C. Reed. 2000. Mitochondrial control of cell death. Nat. Med. 6, 513-519.   DOI
22 Lawen, A. 2003. Apoptosis-an introduction. Bioessays 25, 888-896.   DOI   ScienceOn
23 Lazebnik, Y. A., S. H. Kaufmann, S. Desnoyers, G. G. Poirier, and W. C. Earnshaw. 1994. Cleavage of poly(ADP-ribose) polymerase by a proteinase with properties like ICE. Nature 371, 346-347.   DOI
24 Li, H., H. Zhu, C. J. Xu, and J. Yuan. 1998. Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell 94, 491-501.   DOI
25 Danial, N. N. and S. J. Korsmeyer. 2004. Cell death: critical control points. Cell 116, 205-219.   DOI
26 De Laurenzi, V. and G. Melino. 2000. Apoptosis. The little devil of death. Nature 406, 135-136.   DOI
27 Deveraux, Q. L. and J. C. Reed. 1999. IAP family proteins- suppressors of apoptosis. Genes Dev. 13, 239-252.   DOI
28 Deveraux, Q. L., N. Roy, H. R. Stennicke, T. Van Arsdale, Q. Zhou, S. M. Srinivasula, E. S. Alnemri, G. S. Salvesen, and J. C. Reed. 1998. IAPs block apoptotic events induced by caspase-8 and cytochrome c by direct inhibition of distinct caspases. EMBO J. 17, 2215-2223.   DOI
29 Deveraux, Q. L., R. Takahashi, G. S. Salvesen, and J. C. Reed. 1997. X-linked IAP is a direct inhibitor of cell-death proteases. Nature 388, 300-304.   DOI
30 Fesik, S. W. 2005. Promoting apoptosis as a strategy for cancer drug discovery. Nat. Rev. Cancer 5, 876-885.   DOI
31 Fulda, S. and K. M. Debatin. 2006. Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene 25, 4798-4811.   DOI
32 Gao, Z., Y. Tian, J. Wang, Q. Yin, H. Wu, Y. M. Li, and X. Jiang. 2007. A dimeric Smac/diablo peptide directly relieves caspase-3 inhibition by XIAP. Dynamic and cooperative regulation of XIAP by Smac/Diablo. J. Biol. Chem. 282, 30718-30727.   DOI
33 Gilliland, D. G., C. T. Jordan, and C. A. Felix. 2004. The molecular basis of leukemia. Hematology Am. Soc. Hematol. Educ. Program 80-97.
34 Gupta, S. 2003. Molecular signaling in death receptor and mitochondrial pathways of apoptosis. Int. J. Oncol. 22, 15-20.
35 Hacki, J., L. Egger, L. Monney, S. Conus, T. Rossé, I. Fellay, and C. Borner. 2000. Apoptotic crosstalk between the endoplasmic reticulum and mitochondria controlled by Bcl-2. Oncogene 19, 2286-2295.   DOI
36 Abramson, N. and B. Melton. 2000. Leukocytosis: basics of clinical assessment. Am. Fam. Physician. 62, 2053-2060.
37 Choi, H. J., O. H. Kang, P. S. Park, H. S. Chae, Y. C. Oh, Y. S. Lee, J. G. Choi, G. H. Lee, O. H. Kweon, and D. Y. Kwon. 2007. Mume fructus water extract inhibits pro-inflammatory mediators in lipopolysaccharide-stimulated macrophages. J. Med. Food 10, 460-466.   DOI
38 Ashkenazi, A. and V. M. Dixit. 1999. Apoptosis control by death and decoy receptors. Curr. Opin. Cell Biol. 11, 255-260.   DOI
39 Burlacu, A. 2003. Regulation of apoptosis by Bcl-2 family proteins. J. Cell Mol. Med. 7, 249-257.   DOI
40 Chang, H., H. Lin, L. Yi, J. Zhu, Y. Zhou, M. Mi, and Q. Zhang. 2010. 3,6-Dihydroxyflavone induces apoptosis in leukemia HL-60 cells via reactive oxygen species-mediated p38 MAPK/JNK pathway. Eur. J. Pharmacol. 648, 31-38.   DOI   ScienceOn
41 Chuda, Y., H. Ono, M. Ohnishi-Kameyama, K. Matsumoto, T. Nagata, and Y. Kikuchi. 1999. Mumefural, citric acid derivative improving blood fluidity from fruit-juice concentrate of Japanese apricot (Prunus mume Sieb. et Zucc). J. Agric. Food Chem. 47, 828-831.   DOI
42 Yang, L., Z. Cao, H. Yan, and W. C. Wood. 2003. Coexistence of high levels of apoptotic signaling and inhibitor of apoptosis proteins in human tumor cells: implication for cancer specific therapy. Cancer Res. 63, 6815-6824.
43 Stennicke, H. R. and G. S. Salvesen. 1998. Properties of the caspases. Biochim. Biophys. Acta. 1387, 17-31.   DOI
44 Sun, S. Y., N. Jr Hail, and R. Lotan. 2004. Apoptosis as a novel target for cancer chemoprevention. J. Natl. Cancer Inst. 96, 662-672.   DOI
45 Thomenius, M. J., N. S. Wang, E. Z. Reineks, Z. Wang, and C. W. Distelhorst. 2003. Bcl-2 on the endoplasmic reticulum regulates Bax activity by binding to BH3-only proteins. J. Biol. Chem. 278, 6243-6250.   DOI
46 Yingsakmongkon, S., D. Miyamoto, N. Sriwilaijaroen, K. Fujita, K. Matsumoto, W. Jampangern, H. Hiramatsu, C. T. Guo, T. Sawada, T. Takahashi, K. Hidari, T. Suzuki, M. Ito, Y. Ito, and Y. Suzuki. 2008. In vitro inhibition of human influenza A virus infection by fruit-juice concentrate of Japanese plum (Prunus mume SIEB. et ZUCC). Biol. Pharm. Bull. 31, 511-515.   DOI
47 Peter, M. E. and P. H. Krammer. 2003. The CD95(APO-1/Fas) DISC and beyond. Cell Death Differ. 10, 26-35.   DOI
48 Okada, H., and T. W. Mak. 2004. Pathways of apoptotic and non-apoptotic death in tumour cells. Nat. Rev. Cancer 4, 592-603.   DOI
49 Okada, T., T. Sawada, T. Osawa, M. Adachi, and K. Kubota. 2007. A novel anti-cancer substance, MK615, from ume, a variety of Japanese apricot, inhibits growth of hepatocellular carcinoma cells by suppressing Aurora A kinase activity. Hepatogastroenterology 54, 1770-1774.
50 Oliver, F. J., G. de la Rubia, V. Rolli, M. C. Ruiz-Ruiz, G. de Murcia, and J. M. Murcia. 1998. Importance of poly(ADP-ribose) polymerase and its cleavage in apoptosis. Lesson from an uncleavable mutant. J. Biol. Chem. 273, 33533-33539.   DOI
51 Roy, N., Q. L. Deveraux, R. Takahashi, G. S. Salvesen, and J. C. Reed. 1997. The c-IAP-1 and c-IAP-2 proteins are direct inhibitors of specific caspases. EMBO J. 16, 6914-6925.   DOI
52 Salvesen, G. S., and C. S. Duckett. 2002. IAP proteins: blocking the road to death's door. Nat. Rev. Mol. Cell Biol. 3, 401-410.   DOI