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Food Science and Biotechnology

, Volume 23, Issue 1, pp 269–275 | Cite as

Anti-cancer activity of the ethylacetate fraction from Orostachys japonicus for modulation of the signaling pathway in HepG2 human hepatoma cells

  • Gyeong-Seon Lee
  • Hyeong-Seon Lee
  • Seon-Hee Kim
  • Dong-Hee Suk
  • Deok-Seon Ryu
  • Dong-Seok LeeEmail author
Research Article

Abstract

The molecular mechanisms of the ethylacetate (EtOAc) fraction from Orostachys japonicus (OJE) (including gallic acid, kaempferol, and quercetin) for anti-cancer activities in HepG2 cells were investigated. Apoptosis was detected using morphological observation of nuclear changes and investigation of phosphatidylserine exposure at the cytoplasmic membrane using FITC-Annexin V/PI staining. Activities of the apoptotic factors bcl-2, bax, cytochrome c, pro-caspase-3, 8, and 9, as well as MAPKs levels, were measured using western blotting. Some morphologic features of apoptosis were identified using confocal microscopy. OJE caused the expression of apoptotic proteins to change, as evidenced by an increased bax/bcl-2 ratio and increased expression of cytochrome c, and decreased expressions of pro-caspase-3, 8, and 9. After HepG2 cells were exposed to OJE, expressions of p-JNK and p-ERK1/2 increased in a dose dependent manner. OJE exhibits anti-cancer activity via apoptosis induction through a mitochondria dependent signaling pathway in HepG2 cells.

Keywords

anti-cancer activity Orostachys japonicas apoptotic factors human hepatoma cells 

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References

  1. 1.
    Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, Feuer EJ, Thun MJ. Cancer statistecs, 2005. CA-Cancer J. Clin. 55: 10–30 (2005)CrossRefGoogle Scholar
  2. 2.
    Zhao YY, Shen X, Chao X, Ho CC, Cheng XL, Zhang Y, Lin RC, Du KJ, Luo WJ, Chen JY, Sun WJ. Ergosta-4,6,8(14),22-tetraen-3-one induces G2/M cell cycle arrest and apoptosis in human hepatocellular carcinoma HepG2 cells. Biochim. Biophys. Acta 1810: 384–390 (2011)CrossRefGoogle Scholar
  3. 3.
    Kang SA, Park HJ, Kim MJ, Lee SY, Han SW, Leem KH. Citri reticulatae viride pericarpium extract induced apoptosis in SNU-C4, human colon cancer cells. J. Ethnopharmacol. 97: 231–235 (2005)CrossRefGoogle Scholar
  4. 4.
    Kaufmann SH, Earnshaw WC. Induction of apoptosis by cancer chemotherapy. Exp. Cell Res. 256: 42–29 (2001)CrossRefGoogle Scholar
  5. 5.
    Earnshaw WC, Martins LM, Kaufmann SH. Mammalian caspases: structure, activation, substrates, and functions during apoptosis. Ann. Rev. Biochem. 68: 383–424 (1999)CrossRefGoogle Scholar
  6. 6.
    Han SI, Kim YS, Kim TH. Role of apoptotic and necrotic cell death under physiologic conditions. BMB Rep. 41: 1–10 (2008)CrossRefGoogle Scholar
  7. 7.
    Sun XM, MacFarlane M, Zhuang J, Wolf BB, Green DR, Cohen GM. Distinct caspase cascades are initiated in receptor-mediated and chemical-induced apoptosis. J. Biol. Chem. 274: 5053–5060 (1999)CrossRefGoogle Scholar
  8. 8.
    Brenner B, Koppenhoefer U, Weinstock C, Linderkamp O, Lang F, Gulbins E. Fas- or ceramide-induced apoptosis is mediated by a Rac1-regulated activation of Jun N-terminal kinase/p38 kinases and GADD153. J. Biol. Chem. 272: 22173–22181 (1997)CrossRefGoogle Scholar
  9. 9.
    Schuchmann M, Galle PR. Sensitizing to apoptosis-sharpening the medical sword. J. Hepatol. 40: 335–336 (2004)CrossRefGoogle Scholar
  10. 10.
    Park JC, Han WD, Park JR, Choi SH, Choi JW. Changes in hepatic drug metabolizing enzymes and lipid peroxidation by methanol extract and major compound of Orostacys japonicus. J. Ethnopharmacol. 102: 313–318 (2005)CrossRefGoogle Scholar
  11. 11.
    Jeong Choi SY, Chung MJ, Seo WD, Shin JH, Shon MY, Sung NJ. Inhibitory effects of Orostachys japonicus extracts on the formation of N-Nitrosodimethylamine. J. Agr. Food Chem. 54: 6075–6078 (2006)CrossRefGoogle Scholar
  12. 12.
    Lee JH, Lee SJ, Park S, Kim HK, Jeong WY, Choi JY, Sung NJ, Lee WS, Lim CS, Kim GS, Shin SC. Characterisation of flavonoids in Orostachys japonicus A. Berger using HPLC-MS/MS: Contribution to the overall antioxidant effect. Food Chem. 124: 1627–1633 (2011)CrossRefGoogle Scholar
  13. 13.
    Jeong JH, Ryu DS, Suk DH, Lee DS. Anti-inflammatory effects of ethanol extract from Orostachys japonicus on modulation of signal pathways in LPS-stimulated RAW 264.7 cells. BMB Rep. 44: 399–404 (2011)CrossRefGoogle Scholar
  14. 14.
    Lee HS, Ryu DS, Lee GS, Lee DS. Anti-inflammatory effects of dichloromethane fraction from Orostachys japonicus in RAW 264.7 cells: Suppression of NF-κB activation and MAPK signaling. J. Ethnopharmacol. 140: 271–276 (2011)CrossRefGoogle Scholar
  15. 15.
    Ryu DS, Lee HS, Lee GS, Lee DS. Effects of the ethyl acetate extract of Orostachys japonicus on induction of apoptosis through the p53-mediated signaling pathway in human gastric cancer cells. Biol. Pharm. Bull. 35: 1–6 (2012)CrossRefGoogle Scholar
  16. 16.
    Zhang YX, Kong CZ, Wang HQ, Wang LH, Xu CL, Sun YH. Phosphorylation of Bcl-2 and activation of caspase-3 via the c-Jun N-terminal kinase pathway in ursolic acid-induced DU145 cells apoptosis. Biochimie 91: 1173–1179 (2009)CrossRefGoogle Scholar
  17. 17.
    Yoshida T, Konishi M, Horinaka M, Yasuda T, Goda AE, Taniguchi H, Yano K, Wakada M, Sakai T. Kaempferol sensitizes colon cancer cells to TRAIL-induced apoptosis. Biochem. Biophys. Res. Comm. 375: 129–133 (2008)CrossRefGoogle Scholar
  18. 18.
    Lee DH, Szczepanski M, Lee YJ. Role of Bax in quercetin-induced apoptosis in human prostate cancer cells. Biochem. Pharmacol. 75: 2345–2355 (2008)CrossRefGoogle Scholar
  19. 19.
    Hu W, Kavanagh JJ. Anticancer therapy targeting the apoptotic pathway. Lancet Oncol. 4: 721–729 (2003)CrossRefGoogle Scholar
  20. 20.
    Yu YH, Kuo HP, Hsieh HH, Li JW, Hsu WH, Chen SJ, Su MH, Liu SH, Cheng YC, Chen CY, Kao MC. Ganoderma tsugae induces S phase arrest and apoptosis in doxorubicin-resistant lung adenocarcinoma H23/0.3 Cells via modulation of the PI3K/Akt signaling pathway. Evid. Based Compl. Alt. 2012: 371286 (2012)Google Scholar
  21. 21.
    Rello S, Stocker JC, Moreno V, Gamez A, Pacheco M, Juarranz A, Canete M, Villanuevea A. Morphological criteria to distinguish cell death induced by apoptotic and necrotic treatments. Apoptosis 10: 201–208 (2005)CrossRefGoogle Scholar
  22. 22.
    Gross A, McDonnell JM, Korsmeyer SJ. Bcl-2 family members and the mitochondria in apoptosis. Genes Dev. 13: 1899–1911 (1999)CrossRefGoogle Scholar
  23. 23.
    Scaffidi C, Fulda S, Srinivasan A, Friesen C, Li F, Tomaselli KJ, Debatin KM, Krammer PH, Peter ME. Two CD95 (APO-1/Fas) signaling pathways. EMBO J. 17: 1675–1687 (1998)CrossRefGoogle Scholar
  24. 24.
    Herr I, Debatin KM. Cellular stress response and apoptosis in cancer therapy. Blood 98: 2603–2614 (2001)CrossRefGoogle Scholar
  25. 25.
    Lin HH, Chen JH, Kuo WH, Wang CJ. Chemopreventive properties of Hebiscus Sabdariffa L. on human gastric carcinoma cells through apoptosis induction and JNK/p38 MAPK signaling activation. Chem. Biol. Interact. 165: 59–75 (2007)CrossRefGoogle Scholar
  26. 26.
    Minden A, Karin M. Regulation and function of the JNK subgroup of MAP kinases. Biochim. Biophys. Acta 1333: 85–104 (1997)Google Scholar
  27. 27.
    Xia Z, Dickens M, Raingeaud J, Davis RJ, Greenberg ME. Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 270: 1326–1331 (1995)CrossRefGoogle Scholar
  28. 28.
    Chen YR, Zhou G, Tan TH. c-Jun N-Terminal kinase mediates apoptotic signaling induced by N-(4-hydroxyphenyl) retinamide. Mol. Pharmacol. 56: 1271–1279 (1999)Google Scholar

Copyright information

© The Korean Society of Food Science and Technology and Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Gyeong-Seon Lee
    • 1
    • 2
  • Hyeong-Seon Lee
    • 1
    • 2
  • Seon-Hee Kim
    • 1
    • 2
  • Dong-Hee Suk
    • 1
    • 2
    • 3
  • Deok-Seon Ryu
    • 1
    • 2
  • Dong-Seok Lee
    • 1
    • 2
    Email author
  1. 1.Department of Smart Foods and DrugsInje UniversityGimhae, GyeongnamKorea
  2. 2.Department of Biomedical Laboratory ScienceInje UniversityGimhae GyeongnamKorea
  3. 3.Department of Laboratory MedicineInje University Busan Paik HospitalBusanKorea

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