| |
Dieckol, isolated from the edible brown algae Ecklonia cava, induces apoptosis of ovarian cancer cells and inhibits tumor xenograft growth
- 作者:Ji-Hye Ahn (1) (2)
Yeong-In Yang (1) (2) Kyung-Tae Lee (1) Jung-Hye Choi (1) (2)
1. Department of Life and Nanopharmaceutical Science ; Kyung Hee University ; Seoul ; Republic of Korea 2. Division of Molecular Biology ; College of Pharmacy ; Kyung Hee University ; Dongdaemun-Gu ; Hoegi-Dong ; Seoul ; 130-701 ; Republic of Korea
- 关键词:Apoptosis ; Ecklonia cava ; Dieckol ; Ovarian cancer ; Reactive oxygen species ; Tumor xenograft model
- 刊名:Journal of Cancer Research and Clinical Oncology
- 出版年:2015
- 出版时间:February 2015
- 年:2015
- 卷:141
- 期:2
- 页码:255-268
- 全文大小:1,637 KB
- 参考文献:1. Abdelfadil E et al (2013) Thymoquinone induces apoptosis in oral cancer cells through p38beta inhibition. Am J Chin Med 41:683鈥?96. doi:10.1142/S0192415X1350047X 10.1142/S0192415X1350047X" target="_blank" title="It opens in new window">CrossRef
2. Allavena P et al (2005) Anti-inflammatory properties of the novel antitumor agent yondelis (trabectedin): inhibition of macrophage differentiation and cytokine production. Cancer Res 65:2964鈥?971. doi:10.1158/0008-5472.CAN-04-4037 10.1158/0008-5472.CAN-04-4037" target="_blank" title="It opens in new window">CrossRef 3. Artan M, Li Y, Karadeniz F, Lee SH, Kim MM, Kim SK (2008) Anti-HIV-1 activity of phloroglucinol derivative, 6,6鈥?bieckol, from / Ecklonia cava. Bioorg Med Chem 16:7921鈥?926. doi:10.1016/j.bmc.2008.07.078 10.1016/j.bmc.2008.07.078" target="_blank" title="It opens in new window">CrossRef 4. Athukorala YJW, Vasanthan T, Jeon YJ (2006) An anticoagulative polysaccharide from an enzymatic hydrolysate of / Ecklonia cava. Carbohyd Polym 66:184鈥?91 10.1016/j.carbpol.2006.03.002" target="_blank" title="It opens in new window">CrossRef 5. Balcerczyk A, Soszynski M, Bartosz G (2005) On the specificity of 4-amino-5-methylamino-2鈥?7鈥?difluorofluorescein as a probe for nitric oxide. Free Radic Biol Med 39:327鈥?35. doi:10.1016/j.freeradbiomed.2005.03.017 10.1016/j.freeradbiomed.2005.03.017" target="_blank" title="It opens in new window">CrossRef 6. Cai B, Chang SH, Becker EB, Bonni A, Xia Z (2006) p38 MAP kinase mediates apoptosis through phosphorylation of BimEL at Ser-65. J Biol Chem 281:25215鈥?5222. doi:10.1074/jbc.M512627200 10.1074/jbc.M512627200" target="_blank" title="It opens in new window">CrossRef 7. Cao Y, Adhikari S, Ang AD, Clement MV, Wallig M, Bhatia M (2006) Crambene induces pancreatic acinar cell apoptosis via the activation of mitochondrial pathway. Am J Physiol Gastrointest Liver Physiol 291:G95鈥揋101. doi:10.1152/ajpgi.00520.2005 10.1152/ajpgi.00520.2005" target="_blank" title="It opens in new window">CrossRef 8. Chakrabarti M, Ai W, Banik NL, Ray SK (2013) Overexpression of miR-7-1 increases efficacy of green tea polyphenols for induction of apoptosis in human malignant neuroblastoma SH-SY5Y and SK-N-DZ cells. Neurochem Res 38:420鈥?32. doi:10.1007/s11064-012-0936-5 10.1007/s11064-012-0936-5" target="_blank" title="It opens in new window">CrossRef 9. Conte PF, Cianci C, Gadducci A (1999) Up date in the management of advanced ovarian carcinoma. Crit Rev Oncol Hematol 32:49鈥?8 10.1016/S1040-8428(99)00036-0" target="_blank" title="It opens in new window">CrossRef 10. Cui W et al (2013) Study on inhibitory effect of combined administration of bear bile powder and cyclophosphamide on colorectal cancer liver metastasis by regulating tumor microenvironment. Zhongguo Zhong Yao Za Zhi 38:1036鈥?040 11. Del Mar Blanquer-Rossello M, Oliver J, Valle A, Roca P (2013) Effect of xanthohumol and 8-prenylnaringenin on MCF-7 breast cancer cells oxidative stress and mitochondrial complexes expression. J Cell Biochem. doi:10.1002/jcb.24627 12. Donejko M, Niczyporuk M, Galicka E, Przylipiak A (2013) Anti-cancer properties epigallocatechin-gallate contained in green tea. Postepy Hig Med Dosw 67:26鈥?4 10.5604/17322693.1029528" target="_blank" title="It opens in new window">CrossRef 13. Engel JB et al (2011) Induction of programmed cell death by inhibition of AKT with the alkylphosphocholine perifosine in in vitro models of platinum sensitive and resistant ovarian cancers. Arch Gynecol Obstet 283:603鈥?10. doi:10.1007/s00404-010-1457-6 10.1007/s00404-010-1457-6" target="_blank" title="It opens in new window">CrossRef 14. Fukuyama Y et al (1989) Structure of an anti-plasmin inhibitor, eckol, isolated from the brown alga / Ecklonia kurome Okamura and inhibitory activities of its derivatives on plasma plasmin inhibitors. Chem Pharm Bull (Tokyo) 37:349鈥?53 10.1248/cpb.37.349" target="_blank" title="It opens in new window">CrossRef 15. Gao LJ, Gu PQ, Zhao W, Ding WY, Zhao XQ, Guo SY, Zhong TY (2013) The role of globular heads of the C1q receptor in HPV 16 E2-induced human cervical squamous carcinoma cell apoptosis is associated with p38 MAPK/JNK activation. J Transl Med 11:118. doi:10.1186/1479-5876-11-118 10.1186/1479-5876-11-118" target="_blank" title="It opens in new window">CrossRef 16. Germano G et al (2010) Antitumor and anti-inflammatory effects of trabectedin on human myxoid liposarcoma cells. Cancer Res 70:2235鈥?244. doi:10.1158/0008-5472.CAN-09-2335 10.1158/0008-5472.CAN-09-2335" target="_blank" title="It opens in new window">CrossRef 17. Granado-Serrano AB, Martin MA, Bravo L, Goya L, Ramos S (2006) Quercetin induces apoptosis via caspase activation, regulation of Bcl-2, and inhibition of PI-3-kinase/Akt and ERK pathways in a human hepatoma cell line (HepG2). J Nutr 136:2715鈥?721 18. Green DR, Reed JC (1998) Mitochondria and apoptosis. Science 281:1309鈥?312 10.1126/science.281.5381.1309" target="_blank" title="It opens in new window">CrossRef 19. Gutierrez-Orozco F, Failla ML (2013) Biological activities and bioavailability of mangosteen xanthones: a critical review of the current evidence. Nutrients 5:3163鈥?183. doi:10.3390/nu5083163 10.3390/nu5083163" target="_blank" title="It opens in new window">CrossRef 20. Hausenloy DJ, Yellon DM (2004) New directions for protecting the heart against ischaemia-reperfusion injury: targeting the Reperfusion Injury Salvage Kinase (RISK)-pathway. Cardiovasc Res 61:448鈥?60. doi:10.1016/j.cardiores.2003.09.024 10.1016/j.cardiores.2003.09.024" target="_blank" title="It opens in new window">CrossRef 21. Heo SJ et al (2009) Effect of phlorotannins isolated from / Ecklonia cava on melanogenesis and their protective effect against photo-oxidative stress induced by UV-B radiation. Toxicol In Vitro 23:1123鈥?130. doi:10.1016/j.tiv.2009.05.013 10.1016/j.tiv.2009.05.013" target="_blank" title="It opens in new window">CrossRef 22. Hwang KE et al (2013) Synergistic induction of apoptosis by sulindac and simvastatin in A549 human lung cancer cells via reactive oxygen species-dependent mitochondrial dysfunction. Int J Oncol 43:262鈥?70. doi:10.3892/ijo.2013.1933 23. Inoue M, Sakaguchi N, Isuzugawa K, Tani H, Ogihara Y (2000) Role of reactive oxygen species in gallic acid-induced apoptosis. Biol Pharm Bull 23:1153鈥?157 10.1248/bpb.23.1153" target="_blank" title="It opens in new window">CrossRef 24. Joe MJ, Kim SN, Choi HY, Shin WS, Park GM, Kang DW, Kim YK (2006) The inhibitory effects of eckol and dieckol from Ecklonia stolonifera on the expression of matrix metalloproteinase-1 in human dermal fibroblasts. Biol Pharm Bull 29:1735鈥?739 10.1248/bpb.29.1735" target="_blank" title="It opens in new window">CrossRef 25. Jung WK et al (2009) Inhibitory effects and molecular mechanism of dieckol isolated from marine brown alga on COX-2 and iNOS in microglial cells. J Agric Food Chem 57:4439鈥?446. doi:10.1021/jf9003913 10.1021/jf9003913" target="_blank" title="It opens in new window">CrossRef 26. Jung HA, Jin SE, Ahn BR, Lee CM, Choi JS (2013) Anti-inflammatory activity of edible brown alga Eisenia bicyclis and its constituents fucosterol and phlorotannins in LPS-stimulated RAW264.7 macrophages. Food Chem Toxicol 59:199鈥?06. doi:10.1016/j.fct.2013.05.061 10.1016/j.fct.2013.05.061" target="_blank" title="It opens in new window">CrossRef 27. Kamata H, Hirata H (1999) Redox regulation of cellular signalling. Cell Signal 11:1鈥?4 10.1016/S0898-6568(98)00037-0" target="_blank" title="It opens in new window">CrossRef 28. Kang YH, Lee SJ (2008) The role of p38 MAPK and JNK in Arsenic trioxide-induced mitochondrial cell death in human cervical cancer cells. J Cell Physiol 217:23鈥?3. doi:10.1002/jcp.21470 10.1002/jcp.21470" target="_blank" title="It opens in new window">CrossRef 29. Kang HS, Chung HY, Kim JY, Son BW, Jung HA, Choi JS (2004) Inhibitory phlorotannins from the edible brown alga Ecklonia stolonifera on total reactive oxygen species (ROS) generation. Arch Pharm Res 27:194鈥?98 10.1007/BF02980106" target="_blank" title="It opens in new window">CrossRef 30. Kang KA et al (2005) Triphlorethol-A from / Ecklonia cava protects V79-4 lung fibroblast against hydrogen peroxide induced cell damage. Free Radic Res 39:883鈥?92. doi:10.1080/10715760500161165 10.1080/10715760500161165" target="_blank" title="It opens in new window">CrossRef 31. Kim KK, Lange TS, Singh RK, Brard L, Moore RG (2012) Tetrathiomolybdate sensitizes ovarian cancer cells to anticancer drugs doxorubicin, fenretinide, 5-fluorouracil and mitomycin C. BMC Cancer 12:147. doi:10.1186/1471-2407-12-147 10.1186/1471-2407-12-147" target="_blank" title="It opens in new window">CrossRef 32. Kim SK et al (2008) Effects of / Ecklonia cava ethanolic extracts on airway hyperresponsiveness and inflammation in a murine asthma model: role of suppressor of cytokine signaling. Biomed Pharmacother 62:289鈥?96. doi:10.1016/j.biopha.2007.07.009 10.1016/j.biopha.2007.07.009" target="_blank" title="It opens in new window">CrossRef 33. Kong CS, Kim JA, Yoon NY, Kim SK (2009) Induction of apoptosis by phloroglucinol derivative from / Ecklonia Cava in MCF-7 human breast cancer cells. Food Chem Toxicol 47:1653鈥?658. doi:10.1016/j.fct.2009.04.013 10.1016/j.fct.2009.04.013" target="_blank" title="It opens in new window">CrossRef 34. Korkina LG, Pastore S, Dellambra E, De Luca C (2013) New molecular and cellular targets for chemoprevention and treatment of skin tumors by plant polyphenols: a critical review. Curr Med Chem 20:852鈥?68 35. Kwon SH et al (2011) The neuroprotective effects of Lonicera japonica THUNB. against hydrogen peroxide-induced apoptosis via phosphorylation of MAPKs and PI3K/Akt in SH-SY5Y cells. Food Chem Toxicol 49:1011鈥?019. doi:10.1016/j.fct.2011.01.008 10.1016/j.fct.2011.01.008" target="_blank" title="It opens in new window">CrossRef 36. Kwon TH, Kim TW, Kim CG, Park NH (2013) Antioxidant activity of various solvent fractions from edible brown alga, / Eisenia bicyclis and its active compounds. J Food Sci 78:C679鈥揅684. doi:10.1111/1750-3841.12109 10.1111/1750-3841.12109" target="_blank" title="It opens in new window">CrossRef 37. Lee SHKS, Kang SM, Cha SH, Ahn GN, Um BH, Jeon YJ (2010) Antioxidative effect of / Ecklonia cava dried by far infrared radiating drying. Food Sci Biotechnol 19:129鈥?35 10.1007/s10068-010-0018-x" target="_blank" title="It opens in new window">CrossRef 38. Lee DH, Park MY, Shim BJ, Youn HJ, Hwang HJ, Shin HC, Jeon HK (2012a) Effects of / Ecklonia cava polyphenol in individuals with hypercholesterolemia: a pilot study. J Med Food 15:1038鈥?044. doi:10.1089/jmf.2011.1996 10.1089/jmf.2011.1996" target="_blank" title="It opens in new window">CrossRef 39. Lee SH et al (2012b) Dieckol isolated from / Ecklonia cava protects against high-glucose induced damage to rat insulinoma cells by reducing oxidative stress and apoptosis. Biosci Biotechnol Biochem 76:1445鈥?451 10.1271/bbb.120096" target="_blank" title="It opens in new window">CrossRef 40. Lee SH, Kim JY, Yoo SY, Kwon SM (2013) Cytoprotective effect of dieckol on human endothelial progenitor cells (hEPCs) from oxidative stress-induced apoptosis. Free Radic Res 47:526鈥?34. doi:10.3109/10715762.2013.797080 10.3109/10715762.2013.797080" target="_blank" title="It opens in new window">CrossRef 41. Li X, Liu F, Li Z, Ye N, Huang C, Yuan X (2014) Atractylodes macrocephala polysaccharides induces mitochondrial-mediated apoptosis in glioma C6 cells. Int J Biol Macromol 66:108鈥?12. doi:10.1016/j.ijbiomac.2014.02.019 10.1016/j.ijbiomac.2014.02.019" target="_blank" title="It opens in new window">CrossRef 42. Li Z et al (2013) Pomalidomide shows significant therapeutic activity against CNS lymphoma with a major impact on the tumor microenvironment in murine models. PLoS ONE 8:e71754. doi:10.1371/journal.pone.0071754 10.1371/journal.pone.0071754" target="_blank" title="It opens in new window">CrossRef 43. McCubrey JA et al (2008) Targeting survival cascades induced by activation of Ras/Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways for effective leukemia therapy. Leukemia 22:708鈥?22. doi:10.1038/leu.2008.27 10.1038/leu.2008.27" target="_blank" title="It opens in new window">CrossRef 44. Moscova M, Marsh DJ, Baxter RC (2006) Protein chip discovery of secreted proteins regulated by the phosphatidylinositol 3-kinase pathway in ovarian cancer cell lines. Cancer Res 66:1376鈥?383. doi:10.1158/0008-5472.CAN-05-2666 10.1158/0008-5472.CAN-05-2666" target="_blank" title="It opens in new window">CrossRef 45. Nagayama K, Iwamura Y, Shibata T, Hirayama I, Nakamura T (2002) Bactericidal activity of phlorotannins from the brown alga Ecklonia kurome. J Antimicrob Chemother 50:889鈥?93 10.1093/jac/dkf222" target="_blank" title="It opens in new window">CrossRef 46. Onyango IG, Bennett JP Jr, Tuttle JB (2005) Endogenous oxidative stress in sporadic Alzheimer鈥檚 disease neuronal cybrids reduces viability by increasing apoptosis through pro-death signaling pathways and is mimicked by oxidant exposure of control cybrids. Neurobiol Dis 19:312鈥?22. doi:10.1016/j.nbd.2005.01.026 10.1016/j.nbd.2005.01.026" target="_blank" title="It opens in new window">CrossRef 47. Osone S, Hosoi H, Kuwahara Y, Matsumoto Y, Iehara T, Sugimoto T (2004) Fenretinide induces sustained-activation of JNK/p38 MAPK and apoptosis in a reactive oxygen species-dependent manner in neuroblastoma cells. Int J Cancer 112:219鈥?24. doi:10.1002/ijc.20412 10.1002/ijc.20412" target="_blank" title="It opens in new window">CrossRef 48. Ozcelik B, Turkyilmaz C, Ozgun MT, Serin IS, Batukan C, Ozdamar S, Ozturk A (2010) Prevention of paclitaxel and cisplatin induced ovarian damage in rats by a gonadotropin-releasing hormone agonist. Fertil Steril 93:1609鈥?614. doi:10.1016/j.fertnstert.2009.02.054 10.1016/j.fertnstert.2009.02.054" target="_blank" title="It opens in new window">CrossRef 49. Pal S, Shankar BS, Sainis KB (2013) Cytokines from the tumor microenvironment modulate sirtinol cytotoxicity in A549 lung carcinoma cells. Cytokine 64:196鈥?07. doi:10.1016/j.cyto.2013.07.029 10.1016/j.cyto.2013.07.029" target="_blank" title="It opens in new window">CrossRef 50. Panasyuk A, Frati E, Ribault D, Mitrovic D (1994) Effect of reactive oxygen species on the biosynthesis and structure of newly synthesized proteoglycans. Free Radic Biol Med 16:157鈥?67 10.1016/0891-5849(94)90139-2" target="_blank" title="It opens in new window">CrossRef 51. Park SJ, Jeon YJ (2012) Dieckol from / Ecklonia cava suppresses the migration and invasion of HT1080 cells by inhibiting the focal adhesion kinase pathway downstream of Rac1-ROS signaling. Mol Cells 33:141鈥?49. doi:10.1007/s10059-012-2192-6 10.1007/s10059-012-2192-6" target="_blank" title="It opens in new window">CrossRef 52. Park E et al (2010) Dieckol rescues mice from lethal irradiation by accelerating hemopoiesis and curtailing immunosuppression. Int J Radiat Biol 86:848鈥?59. doi:10.3109/09553002.2010.487011 53. Park SJ, Kim YT, Jeon YJ (2012) Antioxidant dieckol downregulates the Rac1/ROS signaling pathway and inhibits Wiskott-Aldrich syndrome protein (WASP)-family verprolin-homologous protein 2 (WAVE2)-mediated invasive migration of B16 mouse melanoma cells. Mol Cells 33:363鈥?69. doi:10.1007/s10059-012-2285-2 10.1007/s10059-012-2285-2" target="_blank" title="It opens in new window">CrossRef 54. Park GB, Choi Y, Kim YS, Lee HK, Kim D, Hur DY (2013) ROS and ERK1/2-mediated caspase-9 activation increases XAF1 expression in dexamethasone-induced apoptosis of EBV-transformed B cells. Int J Oncol 43:29鈥?8. doi:10.3892/ijo.2013.1949 55. Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, 2002. CA Cancer J Clin 55:74鈥?08 10.3322/canjclin.55.2.74" target="_blank" title="It opens in new window">CrossRef 56. Paszkiewicz M, Budzynska A, Rozalska B, Sadowska B (2012) The immunomodulatory role of plant polyphenols. Postepy Hig Med Dosw 66:637鈥?46 10.5604/17322693.1009908" target="_blank" title="It opens in new window">CrossRef 57. Pelicano H et al (2003) Inhibition of mitochondrial respiration: a novel strategy to enhance drug-induced apoptosis in human leukemia cells by a reactive oxygen species-mediated mechanism. J Biol Chem 278:37832鈥?7839. doi:10.1074/jbc.M301546200 10.1074/jbc.M301546200" target="_blank" title="It opens in new window">CrossRef 58. Riccardi A et al (2005) Combination of trabectedin and irinotecan is highly effective in a human rhabdomyosarcoma xenograft. Anticancer Drugs 16:811鈥?15 10.1097/01.cad.0000172837.67766.6a" target="_blank" title="It opens in new window">CrossRef 59. Ricci JE, Waterhouse N, Green DR (2003) Mitochondrial functions during cell death, a complex (I鈥揤) dilemma. Cell Death Differ 10:488鈥?92. doi:10.1038/sj.cdd.4401225 10.1038/sj.cdd.4401225" target="_blank" title="It opens in new window">CrossRef 60. Sarafraz-Yazdi E, Pincus MR, Michl J (2013) Tumor-targeting peptides and small molecules as anti-cancer agents to overcome drug resistance. Curr Med Chem 61. Shi X, Zhao Y, Jiao Y, Shi T, Yang X (2013) ROS-dependent mitochondria molecular mechanisms underlying antitumor activity of / Pleurotus abalonus acidic polysaccharides in human breast cancer MCF-7 Cells. PLoS ONE 8:e64266. doi:10.1371/journal.pone.0064266 10.1371/journal.pone.0064266" target="_blank" title="It opens in new window">CrossRef 62. Shin HC, Hwang HJ, Kang KJ, Lee BH (2006) An antioxidative and antiinflammatory agent for potential treatment of osteoarthritis from / Ecklonia cava. Arch Pharm Res 29:165鈥?71 10.1007/BF02974279" target="_blank" title="It opens in new window">CrossRef 63. Simamura E, Hirai K, Shimada H, Koyama J, Niwa Y, Shimizu S (2006) Furanonaphthoquinones cause apoptosis of cancer cells by inducing the production of reactive oxygen species by the mitochondrial voltage-dependent anion channel. Cancer Biol Ther 5:1523鈥?529 10.4161/cbt.5.11.3302" target="_blank" title="It opens in new window">CrossRef 64. Singh RK et al (2011) Oral RKS262 reduces tumor burden in a neuroblastoma xenograft animal model and mediates cytotoxicity through SAPK/JNK and ROS activation in vitro. Cancer Biol Ther 11:1036鈥?045 10.4161/cbt.11.12.15706" target="_blank" title="It opens in new window">CrossRef 65. Torres M, Forman HJ (2003) Redox signaling and the MAP kinase pathways. BioFactors 17:287鈥?96 10.1002/biof.5520170128" target="_blank" title="It opens in new window">CrossRef 66. Wang X et al (2011) ROS-activated p38 MAPK/ERK-Akt cascade plays a central role in palmitic acid-stimulated hepatocyte proliferation. Free Radic Biol Med 51:539鈥?51. doi:10.1016/j.freeradbiomed.2011.04.019 10.1016/j.freeradbiomed.2011.04.019" target="_blank" title="It opens in new window">CrossRef 67. Wijesinghe WA, Jeon YJ (2012) Exploiting biological activities of brown seaweed / Ecklonia cava for potential industrial applications: a review. Int J Food Sci Nutr 63:225鈥?35. doi:10.3109/09637486.2011.619965 10.3109/09637486.2011.619965" target="_blank" title="It opens in new window">CrossRef 68. Xing H et al. (2008) Fibronectin-mediated activation of Akt2 protects human ovarian and breast cancer cells from docetaxel-induced apoptosis via inhibition of the p38 pathway. Apoptosis 13:213鈥?23. doi:10.1007/s10495-007-0158-5 10.1007/s10495-007-0158-5" target="_blank" title="It opens in new window">CrossRef 69. Yang YI, Shin HC, Kim SH, Park WY, Lee KT, Choi JH (2012) 6,6鈥?Bieckol, isolated from marine alga / Ecklonia cava, suppressed LPS-induced nitric oxide and PGE(2) production and inflammatory cytokine expression in macrophages: the inhibition of NFkappaB. Int Immunopharmacol 12:510鈥?17. doi:10.1016/j.intimp.2012.01.005 10.1016/j.intimp.2012.01.005" target="_blank" title="It opens in new window">CrossRef 70. Yuan YV, Walsh NA (2006) Antioxidant and antiproliferative activities of extracts from a variety of edible seaweeds. Food Chem Toxicol 44:1144鈥?150. doi:10.1016/j.fct.2006.02.002 10.1016/j.fct.2006.02.002" target="_blank" title="It opens in new window">CrossRef 71. Zanotto-Filho A, Delgado-Canedo A, Schroder R, Becker M, Klamt F, Moreira JC (2010) The pharmacological NFkappaB inhibitors BAY117082 and MG132 induce cell arrest and apoptosis in leukemia cells through ROS-mitochondria pathway activation. Cancer Lett 288:192鈥?03. doi:10.1016/j.canlet.2009.06.038 10.1016/j.canlet.2009.06.038" target="_blank" title="It opens in new window">CrossRef 72. Zhang C, Li Y, Qian ZJ, Lee SH, Li YX, Kim SK (2011) Dieckol from / Ecklonia cava regulates invasion of human fibrosarcoma cells and modulates MMP-2 and MMP-9 expression via NF-kappaB pathway. Evid Based Complem Alternat Med 2011:140462. doi:10.1155/2011/140462 73. Zhao H, Kalivendi S, Zhang H, Joseph J, Nithipatikom K, Vasquez-Vivar J, Kalyanaraman B (2003) Superoxide reacts with hydroethidine but forms a fluorescent product that is distinctly different from ethidium: potential implications in intracellular fluorescence detection of superoxide. Free Radic Biol Med 34:1359鈥?368 10.1016/S0891-5849(03)00142-4" target="_blank" title="It opens in new window">CrossRef 74. Zhou K, Raffoul JJ (2012) Potential anticancer properties of grape antioxidants J. Oncol 2012:803294. doi:10.1155/2012/803294 75. Zinov鈥檈va VN, Spasov AA (2012) Mechanisms of anti-cancer effects of plant polyphenols. II. Suppression on tumor growth. Biomed Khim 58:257鈥?71
- 刊物类别:Medicine
- 刊物主题:Medicine & Public Health
Oncology Cancer Research Internal Medicine Hematology
- 出版者:Springer Berlin / Heidelberg
- ISSN:1432-1335
文摘
Purpose Ecklonia cava is an abundant brown alga and has been reported to possess various bioactive compounds having anti-inflammatory effect. However, the anticancer effects of dieckol, a major active compound in E. cava, are poorly understood. In the present study, we investigated the anti-tumor activity of dieckol and its molecular mechanism in ovarian cancer cells and in a xenograft mouse model . Methods MTT assay, PI staining, and PI and Annexin double staining were performed to study cell cytotoxicity, cell cycle distribution, and apoptosis. We also investigated reactive oxygen species (ROS) production and protein expression using flow cytometry and Western blot analysis, respectively. Anti-tumor effects of dieckol were evaluated in SKOV3 tumor xenograft model. Results We found that the E. cava extract and its phlorotannins have cytotoxic effects on A2780 and SKOV3 ovarian cancer cells. Dieckol induced the apoptosis of SKOV3 cells and suppressed tumor growth without any significant adverse effect in the SKOV3-bearing mouse model. Dieckol triggered the activation of caspase-8, caspase-9, and caspase-3, and pretreatment with caspase inhibitors neutralized the pro-apoptotic activity of dieckol. Furthermore, treatment with dieckol caused mitochondrial dysfunction and suppressed the levels of anti-apoptotic proteins. We further demonstrated that dieckol induced an increase in intracellular ROS, and the antioxidant N-acetyl-l-cysteine (NAC) significantly reversed the caspase activation, cytochrome c release, Bcl-2 downregulation, and apoptosis that were caused by dieckol. Moreover, dieckol inhibited the activity of AKT and p38, and overexpression of AKT and p38, at least in part, reversed dieckol-induced apoptosis in SKOV3 cells. Conclusion These data suggest that dieckol suppresses ovarian cancer cell growth by inducing caspase-dependent apoptosis via ROS production and the regulation of AKT and p38 signaling.
| |
NGLC 2004-2010.National Geological Library of China All Rights Reserved.
Add:29 Xueyuan Rd,Haidian District,Beijing,PRC. Mail Add: 8324 mailbox 100083
For exchange or info please contact us via email.
| |