Advances in Traditional Medicine

Kyung Hee Oriental Medicine Research Center (경희대학교 융합한의과학연구소)
권호 표지
DOI QR코드

DOI QR Code

Ginseng radix induces apoptosis in HL-60 cells and its mechanism as little relation with TNF-α production

  • Koo, Hyun-Na (Department of Pharmacology, College of Oriental Medicine, Kyung Hee University) ;
  • Shin, Soon-Shik (Department of Prescriptionlogy, College of Oriental Medicine, Dongeui University) ;
  • Park, Jin-Han (College of Pharmacy, Wonkwang University) ;
  • Kim, Na-Hyung (College of Pharmacy, Wonkwang University) ;
  • Hong, Seung-Heon (College of Pharmacy, Wonkwang University) ;
  • Kim, Hyung-Min (Department of Pharmacology, College of Oriental Medicine, Kyung Hee University)
  • Published : 2004.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

Ginseng radix, the root of Panax ginseng C. A. Meyer (Araliaceae), is a medicinal plant used world-widely and has been reported to have various biological effects. To investigate the effects of Ginseng radix on HL-60 cell apoptosis, MTT assay, DNA fragmentation assay and flow cytometry were performed on HL-60 cells. Cells were treated with Ginseng radix at different concentrations $(10^{-4},\;10^{-3}\;and\;10^{-2};\;dilution\;rate)$. Ginseng radix significantly induced cells apoptosis with a time- and dose-dependent manner. To determine whether Ginseng radix-induced apoptosis is due to increase of tumor necrosis factor $(TNF-{\alpha})$ secretion, enzyme-linked immunosorbent assay was performed on HL-60 cells. Unexpectedly, Ginseng radix $(96\;{\pm}\;5\;pg/ml)$ significantly decreased the $TNF-{\alpha}$ secretion compared with control $(174\;{\pm}\;14\;pg/ml)$. Furthermore, Ginseng radix with $rIFN-{\gamma}$ synergistically increased nitric oxide production in mouse peritoneal macrophages. Taken together, our data indicate that Ginseng radix induce apoptosis on HL-60 cells without increase of $TNF-{\alpha}$ secretion and could be used for a supplementary remedy of cancer.

Keywords

References

  1. Baek NI, Kim DS, Lee YH, Park JD, Lee CB, Kim SI. (1995) Cytotoxicities of ginseng saponins and their degradation products against some cancer cell lines. Arch. Pharm. Res. 18, 164-168. https://doi.org/10.1007/BF02979189
  2. Bortner CD, Cidlowski JA. (2002) Cellular mechanisms for the repression of apoptosis. Annu. Rev. Pharmacol. Toxicol. 42, 259-281. https://doi.org/10.1146/annurev.pharmtox.42.083101.143836
  3. Choo MK, Park EK, Han MJ, Kim DH. (2003) Antiallergic activity of ginseng and its ginsenosides. Planta Med. 69, 518-522. https://doi.org/10.1055/s-2003-40653
  4. Chung HS, Shin CH, Lee EJ, Hong SH, Kim HM. (2003) Production of nitric oxide and tumor necrosis factor-alpha by Smilacis rhizoma in mouse peritoneal macrophages. Comp. Biochem. Physiol. C Toxicol. Pharmacol. 135, 197-203. https://doi.org/10.1016/S1532-0456(03)00111-X
  5. Dey L, Zhang L, Yuan CS. (2002) Anti-diabetic and anti-obese effects of ginseng berry extract: comparison between intraperitoneal and oral administrations. Am. J. Chin. Med. 30, 645-647. https://doi.org/10.1142/S0192415X02000648
  6. Earnshaw WC. (1995) Nuclear changes in apoptosis. Curr. Opin. Cell Biol. 7, 337-343. https://doi.org/10.1016/0955-0674(95)80088-3
  7. Hajri A, Metzger E, Vallat F, Coffy S, Flatter E, Evrard S, Marescaux J, Aprahamian M. (1998) Role of nitric oxide in pancreatic tumour growth: in vivo and in vitro studies. Br. J. Cancer 78, 841-849. https://doi.org/10.1038/bjc.1998.591
  8. Hibbs JB Jr, Taintor RR, Vavrin Z. (1987) Macrophage cytotoxicity: role for L-arginine deiminase and imino nitrogen oxidation to nitrite. Science 235, 473-476. https://doi.org/10.1126/science.2432665
  9. Keadle TL, Usui N, Laycock KA, Miller JK, Pepose JS, Stuart PM. (2000) IL-1 and TNF-alpha are important factors in the pathogenesis of murine recurrent herpetic stromal keratitis. Invest. Ophthalmol, Vis. Sci. 41, 96-102.
  10. Kim HM, Lee EH, Lim TG, Jung JA, Lyu YS. (1998) Inhibitory effect of Asparagus cochin-chinensis on tumor necrosis factor-alpha secretion from astrocytes. Int. J. Immunopharm. 20, 153-162. https://doi.org/10.1016/S0192-0561(98)00022-8
  11. Koo HN, Hong SH, Song BK, Kim CH, Yoo YH, Kim HM. (2004) Taraxacum officinale induces cytotoxicity through TNF-alpha and IL-1alpha secretion in Hep G2 cells. Life Sci. 74, 1149-1157. https://doi.org/10.1016/j.lfs.2003.07.030
  12. Liu ZQ, Luo XY, Liu GZ, Chen YP, Wang Z C, Sun YX. (2003) In vitro study of the relationship between the structure of ginsenoside and its antioxidative or prooxidative activity in free radical induced hemolysis of human erythrocytes. J. Agric. Food Chem. 51, 2555-2558. https://doi.org/10.1021/jf026228i
  13. Mosmann T. (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods 65, 55-63. https://doi.org/10.1016/0022-1759(83)90303-4
  14. Nascimento FR, Ribeiro-Dias F, Russo M. (1998) Cytotoxic activity of BCG-activated macrophages against L929 tumor cells is nitric oxide-dependent. Braz. J. Med. Biol. Res. 31, 1593-1596.
  15. Nathan C. (1992) Nitric oxide as a secretory product of mammalian cells. FASEB J. 6, 3051-3064. https://doi.org/10.1096/fasebj.6.12.1381691
  16. Neuman MG, Shear NH, Cameron RG, Katz G, Tiribelli C. (1999) Ethanol-induced apoptosis in vitro. Clin. Biochem. 32, 547-555. https://doi.org/10.1016/S0009-9120(99)00054-5
  17. Palmer RM, Ashton DS, Moncada S. (1988) Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature 333, 664-666. https://doi.org/10.1038/333664a0
  18. Titus RG, Sherry B, Cerami A. (1991) The involvement of TNF, IL-1 and IL-6 in the immune response to protozoan parasites. Immunology 12, A13-16.
  19. Ware CF, VanArsdale S, VanArsdale TL. (1996) Apoptosis mediated by the TNF-related cytokine and receptor families. J. Cell Biochem. 60, 47-55. https://doi.org/10.1002/(SICI)1097-4644(19960101)60:1<47::AID-JCB8>3.0.CO;2-3
  20. Weaver SA, Russo MP, Wright KL, Kolios G, Jobin C, Robertson DA, Ward SG. (2001) Regulatory role of phosphatidylinositol 3-kinase on TNF-alpha-induced cyclooxygenase 2 expression in colonic epithelial cells. Gastroenterology 120, 1117-1127. https://doi.org/10.1053/gast.2001.23257