Skip to main content
SpringerLink
Log in

n-butanol fraction of Uncaria rhynchophylla induces apoptosis in human hepatoma cancer cells through activation of PARP

  • Research Paper
  • Published:
Biotechnology and Bioprocess Engineering Aims and scope Submit manuscript

Abstract

The ability of water and ethanolic extracts isolated of Uncaria rhynchophylla (UR) to function as an anticancer agents was studied using HepG2 cells. The ethanolic UR extract was further fractionatedwith hexane, chloroform (CHCl3), ethyl acetate (EtOAc), n-butanol (n-BuOH), and water, and these fractions were subsequently investigated for anticancer activity. Among the fractions, the n-BuOH fraction induced apoptosis in a dose- and time-dependent manner, when determined by cell cycle analysis, Annexin V-FITC/PI double staining, and Hoechst 33342 staining. Moreover, the n-BuOH fraction induced apoptotic cell death by modulating the expression of caspase-7, caspase-8, and poly ADP ribose polymerase (PARP). These results indicated that the n-BuOH fraction from UR has strong anticancer activity in HepG2 cells and causes an upregulation of apoptotic proteins through the activation of PARP.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Refrerences

  1. El-Serag, H. B. and K. L. Rudolph (2007) Hepatocellular carcinoma: Epidemiology and molecular carcinogenesis. Gastroenterol. 132: 2557–2576.

    Article  CAS  Google Scholar 

  2. Llovet, J. M., J. Bruix, and G. J. Gores (2000) Surgical resection versus transplantation for early hepatocellular carcinoma: Clues for the best strategy. Hepatol. 31: 1019–1021.

    Article  CAS  Google Scholar 

  3. Deng, X. K., W. Yin, W. D. Li, F. Z. Yin, X. Y. Lu, X. C. Zhang, Z. C. Huab, and B. C. Cai (2006) The anti-tumor effects of alkaloids from the seeds of Strychnosnux-vomica on HepG2 cells and its possible mechanism. J. Ethnopharmcol. 106: 179–186.

    Article  CAS  Google Scholar 

  4. Granado-Serrano, A. B., M. A. Martin, L. Goya, L. Bravo, and S. Ramos (2009) Timecourse regulation of survival pathways by epicatechin on HepG2 cells. J. Nutr. Biochem. 20: 115–124.

    Article  CAS  Google Scholar 

  5. Ma, X. and Z. Wang (2009) Anticancer drug discovery in the future: An evolutionary perspective. Drug Discov. Today 14: 1136–1142.

    Article  CAS  Google Scholar 

  6. Carelle, N., E. Piotto, A. Bellanger, J. Germanaud, A. Thuillier, and D. Khayat (2002) Changing patient perceptions of the side effects of cancer chemotherapy. Cancer 95: 155–163.

    Article  Google Scholar 

  7. Ndagijimana, A., X. Wang, G. Pan, F. Zhang, H. Feng, and O. Olaleye (2013) A review on indole alkaloids isolated from Uncariarhynchophylla and their pharmacological studies. Fitoterapia 86: 35–47.

    Article  CAS  Google Scholar 

  8. Yang, Q., H. Goto, Y. Shimada, T. Kita, N. Shibahara, and K. Terasawa (2002) Effects of Choto-san on hemorheological factors and vascular function in stroke-prone spontaneously hypertensive rats. Phytomed. 9: 93–98.

    Article  CAS  Google Scholar 

  9. Suk, K., S. Y. Kim, K. Leem, Y. O. Kim, S. Y. Park, J. Hur, J. Baek, K. J. Lee, H. Z. Zheng, and H. Kim (2002) Neuroprotection by methanol extract of Uncariarhynchophylla against global cerebral ischemia in rats. Life Sci. 70: 2467–2480.

    Article  CAS  Google Scholar 

  10. Shimada, Y., H. Goto, T. Itoh, I. Sakakibara, M. Kubo, H. Sasaki, and K. Terasawa (1999) Evaluation of the protective effects of alkaloids isolated from the hooks and stems of Uncariasinensis on glutamate-induced neuronal death in cultured cerebella granule cells from rats. J. Pharm. Pharmacol. 51: 715–722.

    Article  CAS  Google Scholar 

  11. Tang, N. Y., C. H. Liu, S. Y. Su, Y. M. Jan, C. T. Hsieh, C. Y. Cheng, W. C. Shyu, and C. L. Hsieh (2010) Uncariarhynchophylla (miq) Jack plays a role in neuronal protection in kainic acid-treated rats. Am. J. Chin. Med. 38: 251–263.

    Article  Google Scholar 

  12. Deb, D. D., G. Parimala, S. S. Devi, and T. Chakraborty (2011) Effect of thymol on peripheral blood mononuclear cell PBMC and acute promyelotic cancer cell line HL-60. Chem. Biol. Interact. 193: 97–106.

    Article  Google Scholar 

  13. Thornberry, N. A. and Y. Lazebnik (1998) Caspases: Enemies within. Sci. 281: 312–1316.

    Article  Google Scholar 

  14. Eguchi, R., S. Ton, A. Suzuki, Y. Fujimori, T. Nakano, K. Kaji, and T. Ohta (2009) Possible involvement of caspase-6 and-7 but not caspase-3 in the regulation of hypoxia-induced apoptosis in tube-forming endothelial cells. Exp. Cell Res. 315: 327–335.

    Article  CAS  Google Scholar 

  15. Danial, N. N. and S. J. Korsmeyer (2004) Cell death: Critical control points. Cell 116: 205–219.

    Article  CAS  Google Scholar 

  16. Yang, L., X. Liu, Z. Lu, J. Y. W. Chan, L. L. Zhou, K. P. Fung, P. Wu, and S. Wu (2010) Ursolic acid induces doxorubicin-resistant HepG2 cell death via the release of apoptosis-inducing factor. Cancer Lett. 298: 128–138.

    Article  CAS  Google Scholar 

  17. Zheng, D., Y. Wang, D. Zhang, Z. Liu, C. Duan, L. Jia, F. Wang, Y. Liu, G. Liu, L. Hao, and Q. Zhang (2011) In vitro antitumor activity of silybinnano suspension in PC-3 cells. Cancer Lett. 307: 158–164.

    Article  CAS  Google Scholar 

  18. Lee, S. J., E. K. Kim, J. W. Hwang, H. J. Oh, P. J. Park, and C. G. Kim (2009) Antioxidative effects of sulfated chitooligosaccharides on oxidative injury. J. Chitin. Chitosan. 14: 192–196.

    Google Scholar 

  19. Prasad, S., J. Kaur, P. Roy, N. Kalra, and Y. Shukla (2007) Theaflavins induce G2/M arrest by modulating expression of p21waf1/cip1, cdc25C and cyclin B in human prostate carcinoma PC-3 cells. Life Sci. 81: 1323–1331.

    Article  CAS  Google Scholar 

  20. Kim, E. K., S. J. Lee, S. H. Moon, B. T. Jeon, B. K. Kim, T. K. Park, J. S. Han, and P. J. Park (2010) Neuroprotective effects of a novel peptide purified from venison protein. J. Microb. Biotech. 20: 700–707.

    Article  CAS  Google Scholar 

  21. Wang, L., M. L. Xu, J. H. Hu, S. K. Rasmussen, and M. H. Wang (2011) Codonopsislanceolataextract induces G0/G1 arrest and apoptosis in human colon tumor HT-29 cells — Involvement of ROS generation and polyamine depletion. Food Chem. Toxicol. 49: 149–154.

    Article  CAS  Google Scholar 

  22. Rello, S., J. C. Stockert, V. Moreno, A. Gamez, M. Pacheco, A. Juarranz, M. Canete, and A. Villanueva (2005) Morphological criteria to distinguish cell death induced by apoptotic and necrotic treatments. Apoptosis 10: 201–208.

    Article  CAS  Google Scholar 

  23. Earnshaw, W. C., K. Samejima, F. Durrieu, J. Fortune, and N. Osheroff (1999) Role of caspases in apoptotic execution. Biol. Cell. 91: 541–542.

    Article  Google Scholar 

  24. Green, D. R. (1998) Apoptotic pathways: The road to ruin. Cell 94: 695–698.

    Article  CAS  Google Scholar 

  25. Ashktorab, H., M. Neapolitano, C. Bomma, C. Allen, A. Ahmed, A. Dubois, T. Naab, and D. T. Smoot (2002) In vivo and in vitro activation of caspase-8 and-3 associated with Helicobacter pylori infection. Microbes. Infect. 4: 713–722.

    Article  CAS  Google Scholar 

  26. Jimbo, A., E. Fujita, Y. Kouroku, J. Ohnishi, N. Inohara, K. Kuida, K. Sakamaki, S. Yonehara, and T. Momoi (2003) ER stress induces caspase-8 activation, stimulating cytochrome c release and caspase-9 activation. Exp. Cell Res. 283: 156–166.

    Article  CAS  Google Scholar 

  27. Kim, Y. S., J. W. Hwang, S. E. Kim, E. H. Kim, Y. J. Jeon, S. H. Moon, B. T. Jeon, and P. J. Park (2012) Antioxidant activity and protective effects of Uncaria rhynchophylla extracts on t-BHPinduced oxidative stress in Chang cells. Biotechnol. Bioproc. Eng. 17: 1213–1222.

    Article  CAS  Google Scholar 

  28. Zou, J., Q. Chen, X. Jin, S. Tang, K. Chen, T. Zhang, and X. Xiao (2011) Olaquindox induces apoptosis through the mitochondrial pathway in HepG2 cells. Toxicol. 285: 104–113.

    Article  CAS  Google Scholar 

  29. Barnhart, B. C., J. C. Lee, E. C. Alappat, and M. E. Peter (2003) The death effector domain protein family. Oncogene 22: 8634–8644.

    Article  CAS  Google Scholar 

  30. Degterev, A., M. Boyce, and J. Yuan (2003) A decade of caspases. Oncogene 22: 8543–8567.

    Article  CAS  Google Scholar 

  31. Miller, M. A., B. Karacay, X. Zhu, M. S. O’Dorisio, and A. D. Sandler (2006) Caspase 8L a novel inhibitory isoform of caspase 8 is associated with undifferentiated neuroblastoma. Apoptosis 11: 15–24.

    Article  CAS  Google Scholar 

  32. Fulda, S. (2009) Caspase-8 in cancer biology and therapy. Cancer Lett. 281: 128–133.

    Article  CAS  Google Scholar 

  33. Cowling, V. and J. Downward (2002) Caspase-6 is the direct activator of caspase-8 in the cytochrome c-induced apoptosis pathway: Absolute requirement for removal of caspase-6 prodomain. Cell Death Differ. 9: 1046–1056.

    Article  CAS  Google Scholar 

  34. Ame, J. C., V. Rolli, V. Schreiber, C. Niedergang, F. Apiou, P. Decker, S. Muller, T. Hoger, J. Menissier-de Murcia, and G. de Murcia (1999) PARP-2, A novel mammalian DNA damagedependent poly (ADP-ribose) polymerase. J. Biol. Chem. 274: 17860–17868.

    Article  CAS  Google Scholar 

  35. Schreiber, V., J. C. Ame, P. Dolle, I. Schultz, B. Rinaldi, V. Fraulob, J. Menissier-de Murcia, and G. de Murcia (2002) Poly(ADPribose) polymerase-2 (PARP-2) is required for efficient base excision DNA repair in association with PARP-1 and XRCC1. J. Biol. Chem. 277: 23028–23036.

    Article  CAS  Google Scholar 

  36. D’Amours, D., S. Desnoyers, I. D’Silva, and G. G. Poirier (1999) Poly(ADP-ribosyl)ation reactions in the regulation of nuclear functions. Biochem. J. 342: 249–268.

    Article  Google Scholar 

  37. Culmsee, C., C. Zhu, S. Landshamer, B. Becattini, E. Wagner, M. Pellecchia, K. Blomgren, and N. Plesnila (2005) Apoptosisinducing factor triggered by poly(ADP-ribose)polymerase and Bid mediates neuronal cell death after oxygen-glucose deprivation and focal cerebral ischemia. J. Neurosci. 25: 10262–10272.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biotechnology, Konkuk University, Chungju, 380-701, Korea

    Yon-Suk Kim, Jin-Woo Hwang & Pyo-Jam Park

  2. Department of Applied Life science, Konkuk University, Chungju, 380-701, Korea

    Yon-Suk Kim, Jin-Woo Hwang & Pyo-Jam Park

  3. Korea Food Research Institute, Seongnam, 463-746, Korea

    Hyuck-Ju Kwon

  4. Department of Food Bioscience, Research Institute for Biomedical & Health Science, College of Biomedical & Health Science, Konkuk University, Chungju, 380-701, Korea

    Won-Young Lee & Hyuk Song

  5. Department of Food and Biotechnology, Korea National University of Transportation, Chungju, 380-702, Korea

    Jae-Hyun Jeong

  6. Nokyong Research Center, Konkuk University, Chungju, 380-701, Korea

    Si-Heung Sung, Sang-Ho Moon, Byong-Tae Jeon & Pyo-Jam Park

Authors
  1. Yon-Suk Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jin-Woo Hwang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hyuck-Ju Kwon
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Won-Young Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hyuk Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jae-Hyun Jeong
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Si-Heung Sung
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sang-Ho Moon
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Byong-Tae Jeon
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Pyo-Jam Park
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pyo-Jam Park.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kim, YS., Hwang, JW., Kwon, HJ. et al. n-butanol fraction of Uncaria rhynchophylla induces apoptosis in human hepatoma cancer cells through activation of PARP. Biotechnol Bioproc E 19, 411–418 (2014). https://doi.org/10.1007/s12257-013-0644-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12257-013-0644-2

Keywords

Search

Navigation