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Anticancer Potential of an Ethanol Extract of Saussurea Involucrata against Hepatic Cancer Cells in vitro

  • Byambaragchaa, Munkhzaya (Division of Animal Life and Environmental Science, Hankyong National University) ;
  • Cruz, Joseph Dela (Department of Basic Veterinary Sciences, University of the Philippines Los Banos, College Laguna) ;
  • Kh, Altantsetseg (Department of Biotechnology and Breeding, Mongolian State University of Agriculture) ;
  • Hwang, Seong-Gu (Division of Animal Life and Environmental Science, Hankyong National University)
  • Published : 2014.10.11

Abstract

Saussurea involucrata is a Mongolian medicinal plant well known for its effects in promoting blood circulation, and anti-inflammation and analgesic functions. Earlier studies reported that Saussurea involucrata has anticancer activity. The purpose of this study was to confirm the anticancer activity of an ethanol extract of Saussurea involucrata against hepatic cancer and elucidate its mechanisms of action. Hepatocellular carcinoma cells were tested in vitro for cytotoxicity, AO/EB staining for apoptotic cells, apoptotic DNA fragmentation and cell cycle distribution in response to Saussurea involucrata extract (SIE). The mRNA expression of caspase-3,-9 and Cdk2 and protein expression of caspase-3,-9, PARP, XIAP, Cdk2 and p21 were analyzed through real time PCR and Western blotting. Treatment with SIE inhibited HepG2 cell proliferation dose- and time-dependently, but SIE only exerted a modest cytotoxic effect on a viability of Chang human liver cells. Cells exposed to SIE showed typical hallmarks of apoptotic cell death. Cell cycle analysis revealed that SIE caused G1-phase arrest in HepG2 cells. In conclusion, Saussurea involucrata ethanol extract has potential cytotoxic and apoptotic effects on human hepatocellular carcinoma cells. Its mechanism of action might be associated with the inhibition of DNA synthesis, cell cycle (G1) arrest and apoptosis induction through up-regulation of the protein expressions of caspase-3,-9 a nd p21, degradation of PARP and down-regulation of the protein expression of Cdk2 and XIAP.

Keywords

References

  1. Byambaragchaa M, De la Cruz JF, Yang SH, Hwang SG (2013). Anti-metastatic potential of ethanol extract of Saussurea involucrata against hepatic cancer in vitro. Asian Pac J Cancer Prev, 14, 5397-402. https://doi.org/10.7314/APJCP.2013.14.9.5397
  2. Chan SL, Yeo W (2012). Targeted therapy of hepatocellular carcinoma: present and future. J Gastroenterol Hepatol, 27, 862-72. https://doi.org/10.1111/j.1440-1746.2012.07096.x
  3. Dai ZJ, Gao J, Li ZF, et al (2011). In vitro and in vivo antitumor activity of scutellaria barbate extract on murine liver cancer. Molecules, 16, 4389-400. https://doi.org/10.3390/molecules16064389
  4. Desai AG, Qazi GN, Ganju RK, et al (2008). Medicinal plants and cancer chemoprevention. Current Drug Metabolism, 9, 581-91. https://doi.org/10.2174/138920008785821657
  5. Deveraux QL, Roy N, Stennicke HR, et al (1998). IAPs block apoptotic events induced by caspase-8 and cytochrome c by direct inhibition of distinct caspases. EMBO J, 17, 2215-23. https://doi.org/10.1093/emboj/17.8.2215
  6. Dong F, Guo W, Zhang L, et al (2006). Downregulation of XIAP and induction of apoptosis by the synthetic Cdk inhibitor GW8510 in Non-small cell lung cacer cells. Cancer Biol Ther, 5, 165-70. https://doi.org/10.4161/cbt.5.2.2316
  7. Erol A (2011). Genotoxic stress-mediated cell cycle activities for the decision of cellular fate. Cell Cycle, 10, 3239-48. https://doi.org/10.4161/cc.10.19.17460
  8. George S, Bhalerao SV, Lidstone EA, et al (2010). Cytotoxicity screening of Bangladeshi medicinal plant extracts on pancreatic cancer cells. MCC Complement Altern Med, 10, 52. https://doi.org/10.1186/1472-6882-10-52
  9. Guo B, Gao M, Liu CZ (2007). In vitro propagation of an endangered medicinal plant Saussurea involucrata Kar. et Kir. Plant Cell Reports, 26, 261-5. https://doi.org/10.1007/s00299-006-0230-6
  10. Huang CC, Wu MC, Xu GW, et al (1992). Overexpression of the MDR1 gene and P-glycoprotein in human hepatocellular carcinoma. J Natl Cancer Inst, 84, 262-4. https://doi.org/10.1093/jnci/84.4.262
  11. Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clini, 61, 69-90. https://doi.org/10.3322/caac.20107
  12. Jia JM, Wu CF, Liu W, et al (2005). Antiinflammatory and analgesic activities of the tissue culture of Saussurea involucrata. Biol Pharm Bull, 28, 1612-4. https://doi.org/10.1248/bpb.28.1612
  13. Khan M, Yu B, Rasul A, et al (2012). Jaceosidin induces apoptosis in U87 glioblastoma cells through G2/M phase arrest. eCAM: Evid Based Complement Altern Med, 2012, 703034.
  14. Li GH, Fa L, Zhao RC (1989). Studies on pharmacological actions of Saussurea involucrata Kar. et Kir. Acta Pharm Sinic, 15, 368-9.
  15. Li FX, Jin ZP, Zhao DX, et al (2006). Overexpression of the Saussurea medusa chalcone isomerase gene in S. involucrata hairy root cultures enhances their biosynthesis of apigenin. Phytochemistry, 67, 553-60. https://doi.org/10.1016/j.phytochem.2005.12.004
  16. Li ZF, Wang ZD, Ji YY, et al (2009). Induction of apoptosis and cell cycle arrest in human HCC MHCC97H cells with chrysanthemum indicum extract. World J Gastroenterol, 15, 4538-46. https://doi.org/10.3748/wjg.15.4538
  17. Li-Weber M (2013). Targeting apoptosis pathways in cancer by Chinese medicine. Cancer Letters, 332, 304-12. https://doi.org/10.1016/j.canlet.2010.07.015
  18. Liu L, Xiao X, Zhang L (1985). Effect of the flavonoids from Saussurea involucrata on DNA synthesis of cancer cells. J Lanzhou University Nat Sci, 21, 80-3.
  19. Lu CX, Nan KJ, Nie YL, et al (2010). Delisheng, a Chinese medicinal compound, exerts anti-proliferative and proapoptotic effects on HepG2 cells through extrinsic and intrinsic pathways. Mol Biol Rep, 37, 3407-12. https://doi.org/10.1007/s11033-009-9930-7
  20. Masgras I, Carrera S, de Verdier PJ, et al (2012). Reactive oxygen species and mitochondrial sensitivity to oxidative stress determine induction of cancer cell death by p21. J Biol Chem, 287, 9845-54. https://doi.org/10.1074/jbc.M111.250357
  21. Mukherjee AK, Basu S, Sarkar N, et al (2011). Advances in cancer therapy with plant based natural products. Curr Med Chem, 8, 1467-86.
  22. Nurse P (2000). A long twentieth century of the cell cycle and beyond. Cell, 100, 71-8. https://doi.org/10.1016/S0092-8674(00)81684-0
  23. Padhya KT, Marrero JA, Singal AG (2013). Recent advances in the treatment of hepatocellular carcinoma. Curr Opin Gastroenterol, 29, 285-92. https://doi.org/10.1097/MOG.0b013e32835ff1cf
  24. Roomi MW, Roomi NW, Kalinovsky T, et al (2010). In vivo and In vitro effect of a nutrient mixture on human hepatocarcinoma cell line SK-HEP-1. Exp Oncol, 32, 84-91.
  25. Salvesen GS, Duckett CS (2002). IAP proteins: blocking the road to death's door. Nature Rev Mol Cell Biol, 3, 401-10. https://doi.org/10.1038/nrm830
  26. Shynu M, Gupta PK, Saini M (2011). Antineoplastic potential of medicinal plants. Recent Pat Biotechnol, 5, 85-94. https://doi.org/10.2174/187220811796365662
  27. Sigstedt SC, Hooten CJ, Callewaert MC, et al (2008). Evaluation of aqueous extracts of taraxacum officinale on growth and invasion of breast and prostate cancer cells. Int J Oncol, 32, 1085-090.
  28. Sreelatha S, Jeyachitra A, Padma PR (2011). Antiproliferation and induction of apoptosis by Moringa oleifera leaf extract on human cancer cells. Food Chem Toxicol, 49, 1270-5. https://doi.org/10.1016/j.fct.2011.03.006
  29. Sun B, Geng S, Huang X, et al (2011). Coleusin factor exerts cytotoxic activity by inducing G0/G1 cell cycle arrest and apoptosis in human gastric cancer BGC-823 cells. Cancer Lett, 301, 95-105. https://doi.org/10.1016/j.canlet.2010.10.010
  30. Takahashi R, Deveraux Q, Tamm I, et al (1998). A single BIR domain of XIAP sufficient for inhibiting caspases. J Biol Chem, 273, 7787-90. https://doi.org/10.1074/jbc.273.14.7787
  31. Van den Heuvel S, Harlow E (1993). Distinct roles for cyclindependent kinases in cell cycle control. Science, 262, 2050-4. https://doi.org/10.1126/science.8266103
  32. Wang S, Hu Y, Tan W, et al (2012). Compatibility art of traditional Chinese medicine: from the perspective of herb pairs. J Ethnopharmacol, 143, 412-23. https://doi.org/10.1016/j.jep.2012.07.033
  33. Way TD, Lee JC, Kuo DH, et al (2010). Inhibition of epidermal growth factor receptor signaling by Saussurea involucrata, a rare traditional Chinese medicinal herb, in human hormoneresistant prostate cancer PC-3 Cells. J Agricultural Food Chem, 58, 3356-65. https://doi.org/10.1021/jf903793p
  34. Zhang H, Xiong Y, Beach D (1993). Proliferating cell nuclear antigen and p21 are components of multiple cell cycle kinase complexes. Mol Biol Cell, 4, 89-906.

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