Antitumor Effect of Hang-Am-Dan Non-boiled Water Extracts on NCI-H460 Tumor Regression Model

  • Kim, Jun-Lae (East-West Cancer Center, Dunsan Oriental Hospital of Daejeon University) ;
  • Kim, Kyung-Soon (East-West Cancer Center, Dunsan Oriental Hospital of Daejeon University) ;
  • Park, Jae-Woo (East-West Cancer Center, Dunsan Oriental Hospital of Daejeon University) ;
  • Lee, Yeon-Weol (East-West Cancer Center, Dunsan Oriental Hospital of Daejeon University) ;
  • Cho, Chong-Kwan (East-West Cancer Center, Dunsan Oriental Hospital of Daejeon University) ;
  • Yoo, Hwa-Seung (East-West Cancer Center, Dunsan Oriental Hospital of Daejeon University)
  • Received : 2010.02.17
  • Accepted : 2010.05.03
  • Published : 2010.05.30

Abstract

Objective: This experimental study was performed to examine if Hang-Am-Dan non-boiled water extracts (HAD-N) induce apoptosis in human lung carcinoma NCI-H460 cells in vitro and inhibits the growth of NCI-H460 cell-transplanted solid tumor in vivo. Materials and Methods: We cultured NCI-H460 cell lines and xenografted them to nude mice. The mice were divided into 3 groups, NCI-H460 cell alone, NCI-H460 + 90 mg/kg HAD-N treated group, and NCI-H460 + 180 mg/kg HAD-N treated group, with seven mice per group. HAD-N was orally administrated every day for four weeks. We checked their body weight and tumor weight and volumes two times a week and their absolute organ weight and biochemical blood analysis at the final day by sacrificing them. We also calculated their tumor inhibition rate (IR), mean survival time and percent increase in life span (% ILS). Results: In this study, we observed that all of the HAD-N treated mice got smaller tumors. The more doses of HAD-N used, the less IR showed at the 8th day after starting this experiment. Tumor weight and volume of HAD-N treatment groups also decreased. Mean survival time and percent increase in life span (% ILS) in the high-dose HAD-N treatment groups were higher than those of other groups. The test substances in the blood level UN results showed reduction in the significance in both HAD-N 90 mg/kg and HAD-N 180 mg/kg (p<0.01). The blood level phosphatase results in HAD-N 90 mg/kg group compared to NCI-H460 cell alone group showed a reduction in significance (p<0.05). AST levels HAD-N 180 mg/kg group compared to NCI-H460 cell alone group significance as well (p<0.05). Conclusion: We suggest that the results of the in vivo study showed that HAD-N may have potential as a growth inhibitor of tumor-induced NCI-H460 of nude mice in spite of the shortcomings of this study. More studies to overcome those shortcomings and to find out significant antitumor mechanism will be needed.

Keywords

References

  1. Carney DN. Lung cancer: time to move on from chemotherapy. N. Engl. J. Med. 2002; 346(2): 126-8. https://doi.org/10.1056/NEJM200201103460211
  2. Herbst RS, Heymach JV, Lippman SM. Lung cancer. N. Engl. J. Med. 2008; 359(13):1367-80. https://doi.org/10.1056/NEJMra0802714
  3. Singhal S, Vachani A, Antin-Ozerkis D, Kaiser LR, Albelda SM. Prognostic implications of cell cycle, apoptosis, and angiogenesis biomarkers in non-small cell lung cancer: a review. Clin. Cancer Res. 2005; 11(11):3974-86. https://doi.org/10.1158/1078-0432.CCR-04-2661
  4. Park SC, Yoo HS, Park C, Cho CK, Kim GY, Kim WJ, et al. Induction of apoptosis in human lung carcinoma cells by the water extract of Panax notoginseng is associated with the activation of caspase-3 through downregulation of Akt. International Journal of Oncology. 2009; 35(1): 121-7.
  5. Park SE, Yoo HS, Jin CY, Hong SH, Lee YW, Kim BW, et al. Induction of apoptosis and inhibition of telomerase activity in human lung carcinoma cells by the water extract of Cordyceps militaris. Food and Chemical Toxicology. 2009; 47(7):1667-75. https://doi.org/10.1016/j.fct.2009.04.014
  6. Yoo HS, Cho CK, Michael S, Hong BS. Review of the Best Case Series Methodology: Best Case Series Results of East-West Cancer Center. Integrative Cancer Therapies. 2008; 7(3):182-8. https://doi.org/10.1177/1534735408322844
  7. Lee W, Choi HI, Kim MJ, Park SY. Depletion of mitochondrial DNA up-regulates the expression of MDR1 gene via an increase in mRNA stability. Exp Mol Med. 2008; 40(1):109-17. https://doi.org/10.3858/emm.2008.40.1.109
  8. Kim HM, Lim JS, Park SK, Kang JS, Lee KH, Lee CW, et al. Antitumor activity of cytokineinduced killer cells against human lung cancer. International Immunopharmacology. 2007; 7(13) :1802-7. https://doi.org/10.1016/j.intimp.2007.08.016
  9. Chai HY, Sin JS, Kim TM, Kwon W, Cho YM, Choi EK, et al. Antitumor activity of K6, an allylthiopyridazine derivative, in Hep-$G_{2}$ cellstransplanted nude mice. Kor. J. of Lab Ani Sci. 2004; 20(1):1-10.
  10. Teicher BA. Anticancer Drug Development Guide. Humana Press, New Jersey. 1997:91-7.
  11. Yang EB, Tang WY, Zhang K, Cheng LY, Mack POP. Norcantharidin inhibits growth of human Hep$G_{2}$ cell-transplanted tumor in nude mice and prolongs host survival. Cancer Lett. 1997; 117 (1):93-8. https://doi.org/10.1016/S0304-3835(97)00206-1
  12. Ghobrial IM, Witzig TE, Adjei AA. Targeting apoptosis pathways in cancer therapy. CA Cancer J Clin. 2005; 55(3):178-94 https://doi.org/10.3322/canjclin.55.3.178
  13. Han SI, Kim YS, Kim TH. Role of apoptotic and necrotic cell death under physiologic conditions. BMB Rep. 2008; 41(1):1-10. https://doi.org/10.5483/BMBRep.2008.41.1.001
  14. Earnshaw WC, Martins LM, Kaufmann SH. Mammalian caspases: structure, activation, substrates, and functions during apoptosis. Annu. Rev. Biochem. 1999; 68:383-424. https://doi.org/10.1146/annurev.biochem.68.1.383
  15. Adams JM, Cory S. Life-or-death decisions by the Bcl-2 protein family. Trends Biochem. Sci. 2001; 26(1):61-6. https://doi.org/10.1016/S0968-0004(00)01740-0
  16. Stennicke HR, Salvesen GS. Properties of the caspases. Biochim. Biophys. Acta. 1998; 1387 (1-2):17-31.
  17. Hengartner MO. The biochemistry of apoptosis. Nature. 2000; 407(6805):770-6. https://doi.org/10.1038/35037710
  18. Nagata S, Golstein P. The Fas death factor. Science. 1996; 267(5203):1449-56.
  19. Jiang C, Yang YF, Cheng SH. Fas ligand gene therapy for vascular intimal hyperplasia. Curr. Gene Ther. 2004; 4(1):33-9. https://doi.org/10.2174/1566523044578022
  20. Jeong SY, Seol DW. The role of mitochondria in apoptosis. BMB Rep. 2008; 41(1):11-22. https://doi.org/10.5483/BMBRep.2008.41.1.011
  21. Mow BM, Blajeski AL, Chandra J, Kaufmann SH. Apoptosis and the response to anticancer therapy. Curr Opin Oncol. 2001; 13(6):453-62. https://doi.org/10.1097/00001622-200111000-00007
  22. Mohamad N, Gutiérrez A, Nunez M, Cocca C, Martín G, Cricco G, et al. Mitochondrial apoptotic pathways. Biocell. 2005; 29(2):149-61.
  23. Murphy AN, Bredesen DE, Cortopassi G, Wang E, Fiskum G. Bcl-2 potentiates the maximal calcium uptake capacity of neural cell mitochondria. Proc Natl Acad Sci U S A. 1996; 93(18):9893-8. https://doi.org/10.1073/pnas.93.18.9893
  24. Kluck RM, Bossy-Wetzel E, Green DR, Newmeyer DD. The release of cytochrome C from mitochondria: a primary site for Bcl-2 regulation of apoptosis. Science. 1997; 275(5303) :1132-6. https://doi.org/10.1126/science.275.5303.1132
  25. Thees S, Hubbard GB, Winckler J, Schultz C, Rami A. Specific alteration of the Bax/Bcl2 ratio and cytochrome C without execution of apoptosis in the hippocampus of aged baboons. Restor Neurol Neurosci. 2005 23(1):1-9.
  26. Zinkel S, Gross A, Yang E. BCL2 family in DNA damage and cell cycle control. Cell Death Differ. 2006; 13(8):1351-9. https://doi.org/10.1038/sj.cdd.4401987
  27. Chung VQ, Tattersall M, Cheung HT. Interactions of a herbal combination that inhibits growth of prostate cancer cells. Cancer Chemother Pharmacol. 2004; 53(5):384-90. https://doi.org/10.1007/s00280-003-0746-1