대한한의학회지 (The Journal of Korean Medicine)

  • 제30권6호
  • /
  • Pages.17-26
  • /
  • 2009
  • /
  • 1010-0695(pISSN)
  • /
  • 2288-3339(eISSN)
대한한의학회 (The Society of Korean Medicine)
권호 표지

Effect of Lycii cortex radicis Extraction on Glioma Cell Viability

  • Kim, Seang-Jae (Dept. of Internal Medicine, College of Korean Medicine, Dongguk University) ;
  • Jeong, Ji-Cheon (Dept. of Internal Medicine, College of Korean Medicine, Dongguk University)
  • 발행 : 2009.11.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Objectives: Little information is available regarding the effect of Lycii cortex radicis (LCR) on cell viability in glioma cells. This study was therefore undertaken to examine the effect of LCR on cell survival in U87MG human glioma cells. Methods: Cell viability and cell death were estimated by MTT assay and trypan blue exclusion assay, respectively. Reactive oxygen species (ROS) generation was measured using the fluorescence probe DCFH-DA. Activation of Akt and extracellular signal-regulated kinase (ERK) and activation of caspase-3 were estimated by Western blot analysis. Results: LCR resulted in apoptotic cell death in a dose- and time-dependent manner. LCR increased reactive oxygen species (ROS) generation and LCR-induced cell death was also prevented by antioxidants, suggesting that ROS generation played a critical role in LCR-induced cell death. Western blot analysis showed that LCR treatment caused down-regulation of Akt and ERK. The LCR-induced cell death was increased by the inhibitors of Akt and ERK. Activation of caspase-3 was stimulated by LCR and caspase inhibitors prevented the LCR-induced cell death. Conclusion: These findings suggest that LCR results in human glioma cell death through a mechanism involving ROS generation, down-regulation of Akt and ERK, and caspase activation.

키워드

참고문헌

  1. Ohgaki H, Kleihues P. Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas. J Neuropathol Exp Neurol. 2005; 64:479-89. https://doi.org/10.1093/jnen/64.6.479
  2. Surawicz TS, Davis F, Freels S, Laws ER Jr, Menck HR. Brain tumor survival: results from the National Cancer Data Base. J Neurooncol. 1998; 40:151-60. https://doi.org/10.1023/A:1006091608586
  3. DeAngelis LM. Brain tumors. N Engl J Med. 2001; 344:114-23. https://doi.org/10.1056/NEJM200101113440207
  4. Sanai N, Alvarez-Buylla A, Berger MS. Neural stem cells and the origin of gliomas. N Engl J Med. 2005;353:811-22. https://doi.org/10.1056/NEJMra043666
  5. Feng R, Lu Y, Bowman LL, Qian Y, Castranova V, Ding M. Inhibition of activator protein-1, NF-kappaB, and MAPKs and induction of phase 2 detoxifying enzyme activity by chlorogenic acid. J Biol Chem. 2005; 280:27888-95. https://doi.org/10.1074/jbc.M503347200
  6. Feng R, Ni HM, Wang SY, Tourkova IL, Shurin MR, Harada H, et al. Cyanidin-3-rutinoside, a natural polyphenol antioxidant, selectively kills leukemic cells by induction of oxidative stress. J Biol Chem. 2007; 282:13468-76. https://doi.org/10.1074/jbc.M610616200
  7. Surh YJ. Cancer chemoprevention with dietary phytochemicals. Nat Rev Cancer. 2003; 3:768-80. https://doi.org/10.1038/nrc1189
  8. Lee SI. Herbs. Seoul:Medical Herb Co. 1983:133-4.
  9. Ye Z, Huang Q, Ni HX, Wang D. Cortex Lycii Radicis extracts improve insulin resistance and lipid metabolism in obese-diabetic rats. Phytother Res. 2008; 22:1665-70. https://doi.org/10.1002/ptr.2552
  10. Denizot F, Lang R. Rapid colorimetric assay for cell growth and survival: Modifications to the tetrazolium dye procedure giving improved sensitivity and reliability. J Immunol Methods. 1986; 89:271-7. https://doi.org/10.1016/0022-1759(86)90368-6
  11. Cobb MH. MAP kinase pathways. Prog Biophys Mol Biol. 1999; 71:479-500. https://doi.org/10.1016/S0079-6107(98)00056-X
  12. Coffer PJ, Jin J, Woodgett JR. Protein kinase B (c-Akt): a multifunctional mediator of phosphatidylinositol 3-kinase activation. Biochem J. 1998; 335(Pt 1):1-13. https://doi.org/10.1042/bj3350001
  13. Xia Z, Dickens M, Raingeaud J, Davis RJ, Greenberg ME. Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science. 1995; 270:1326-31. https://doi.org/10.1126/science.270.5240.1326
  14. Cohen GM. Caspases: the executioners of apoptosis. Biochem J. 1997; 326:1-16. https://doi.org/10.1042/bj3260001
  15. Ramos S. Effects of dietary flavonoids on apoptotic pathways related to cancer chemoprevention. J Nutr Biochem. 2007; 18:427-42. https://doi.org/10.1016/j.jnutbio.2006.11.004
  16. Ren W, Qiao Z, Wang H, Zhu L, Zhang L. Flavonoids: promising anticancer agents. Med Res Rev. 2003; 23:519-34. https://doi.org/10.1002/med.10033
  17. Seong NK, Kim SH, Seo YB, Oh AH. Effects of Lycii Radicis Cortex and Lycii Cortex on the change of blood sugar, blood pressure, hemato-logical and antipyretic action in rat. Kor J Herbol, 1994; 9:161-71.
  18. Lee BO, Jeong EJ, Park SO. The screening of antiallergic herbs suppressing egg and milk allergy. Kor J Dair Sci, 1994; 16:343-53.
  19. Cho HS, The effect of Lycium spp. on the hyperlipidemia and the hypertension in rat. Ph.D. thesis, Graduate School of Kyung Hee University. 2006.
  20. Ahn BY, Gwak JS, Ryu SH, Moon GS, Choi DS, Park SH, Han JH. Protective effect of water extract of Lycii Cortex Radicis on lipid peroxidation of rat skin exposed to ultraviolet B radiation. J Kor Agr Chem Soc. 2002; 45:218-22.
  21. Miura YH, Tomita I, Watanabe T, Hirayama T, Fukui S. Active oxygens generation by flavonoids. Biol Pharm Bull. 1998; 21:93-6. https://doi.org/10.1248/bpb.21.93
  22. Shen SC, Ko CH, Tseng SW, Tsai SH, Chen YC. Structurally related antitumor effects of flavanones in vitro and in vivo: involvement of caspase 3 activation, p21 gene expression, and reactive oxygen species production. Toxicol Appl Pharmacol. 2004; 197:84-95. https://doi.org/10.1016/j.taap.2004.02.002
  23. Wang IK, Lin-Shiau SY, Lin JK. Induction of apoptosis by apigenin and related flavonoids through cytochrome c release and activation of caspase-9 and caspase-3 in leukaemia HL-60 cells. Eur J Cancer. 1999; 35:1517-25. https://doi.org/10.1016/S0959-8049(99)00168-9
  24. Chen YC, Shen SC, Chow JM, Ko CH, Tseng SW. Flavone inhibition of tumor growth via apoptosis in vitro and in vivo. Int J Oncol. 2004; 25:661-70.
  25. Bhaskara VK, Sundaram C, Babu PP. pERK, pAkt and pBad: a possible role in cell proliferation and sustained cellular survival during tumorigenesis and tumor progression in ENU induced transplacental glioma rat model. Neurochem Res. 2006; 31:116370. https://doi.org/10.1007/s11064-006-9142-7
  26. Jacques-Silva MC, Bernardi A, Rodnight R, Lenz G. ERK, PKC and PI3K/Akt pathways mediate extracellular ATP and adenosine-induced proliferation of U138-MG human glioma cell line. Oncology. 2004; 67:450-9. https://doi.org/10.1159/000082930
  27. Wang L, Liu F, Adamo ML. Cyclic AMP inhibits extracellular signal-regulated kinase and phosphatidylinositol 3-kinase/Akt pathways by inhibiting Rap1. J Biol Chem. 2001; 276:37242-9. https://doi.org/10.1074/jbc.M105089200
  28. Wong ML, Kaye AH, Hovens CM. Targeting malignant glioma survival signalling to improve clinical outcomes. J Clin Neurosci. 2007; 14:301-8. https://doi.org/10.1016/j.jocn.2006.11.005
  29. Chekenya M, Krakstad C, Svendsen A, Netland IA, Staalesen V, Tysnes BB, et al. The progenitor cell marker NG2/MPG promotes chemoresistance by activation of integrin-dependent PI3K/Akt signaling. Oncogene. 2008; 27:5182-94. https://doi.org/10.1038/onc.2008.157
  30. Knobbe CB, Merlo A, Reifenberger G. Pten signaling in gliomas. Neuro Onco. 2002; 4:196-211. https://doi.org/10.1215/15228517-4-3-196
  31. Opel D, Westhoff MA, Bender A, Braun V, Debatin KM, Fulda S. Phosphatidylinositol 3-kinase inhibition broadly sensitizes glioblastoma cells to death receptor-and drug-induced apoptosis. Cancer Res. 2008; 68:6271-80. https://doi.org/10.1158/0008-5472.CAN-07-6769
  32. Pearson G, Robinson F, Beers Gibson T, Xu BE, Karandikar M, Berman K, et al. Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev. 2001; 22:153-83. https://doi.org/10.1210/er.22.2.153
  33. Brunet A, Pages G, Pouyssegur J. Constitutively active mutants of MAP kinase (MEK1) induce growth factor-relaxation and oncogenicity when expressed in fibroblasts. Oncogene. 1994; 9:3379-87.
  34. Groom LA, Sneddon AA, Alessi DR, Dowd S, Keyse SM. Differential regulation of the MAP, SAP and RK/p38 kinases by Pyst1, a novel cytosolic dual-specificity phosphatase. Embo J. 1996; 15:3621-32.
  35. Kortenjann M, Thomae O, Shaw PE. Inhibition of v-raf-dependent c-Fos expression and transformation by a kinase-defective mutant of the mitogen-activated protein kinase Erk2. Mol Cell Biol. 1994; 14:4815-24. https://doi.org/10.1128/MCB.14.7.4815
  36. Moon SK, Cho GO, Jung SY, Gal SW, Kwon TK, Lee YC, et al. Quercetin exerts multiple inhibitory effects on vascular smooth muscle cells: role of ERK1/2, cell-cycle regulation, and matrix metalloproteinase-9. Biochem Biophys Res Commun. 2003; 301:1069-78. https://doi.org/10.1016/S0006-291X(03)00091-3
  37. Singh RP, Tyagi AK, Zhao J, Agarwal R. Silymarin inhibits growth and causes regression of established skin tumors in SENCAR mice via modulation of mitogen-activated protein kinases and induction of apoptosis. Carcinogenesis. 2002; 23:499-510. https://doi.org/10.1093/carcin/23.3.499
  38. Spencer JP, Rice-Evans C, Williams RJ. Modulation of pro-survival Akt/protein kinase B and ERK1/2 signaling cascades by quercetin and its in vivo metabolites underlie their action on neuronal viability. J Biol Chem. 2003; 278:34783-93. https://doi.org/10.1074/jbc.M305063200
  39. Nguyen TT, Tran E, Nguyen TH, Do PT, Huynh TH, Huynh H. The role of activated MEK-ERK pathway in quercetin-induced growth inhibition and apoptosis in A549 lung cancer cells. Carcinogenesis. 2004; 25:647-59. https://doi.org/10.1093/carcin/bgh052