Ginsenoside Rb1이 C6 Glioma 세포주의 Nitric Oxide 생성과 세포자멸사에 미치는 효과 = The Effects of Ginsenoside Rb1 on the Apoptosis and the Production of Nitric Oxide in Rat C6 Glioma Cells

다국어 초록 (Multilingual Abstract)

Background : Ginsenosides, the extract of Panax ginseng, exert various pharmacological
effects such as anticancer activity by the mechanism that is not yet defined. In this study, we
proposed that the anticancer effect of ginsenoside Rb1 is related to tumor cell apoptosis and
ginsenoside Rb1 induces the tumor cell apoptosis via the nitric oxide (NO) production. Methods
: Rat C6 glioma cells were activated by treating with lipopolysaccharide (LPS), interferon
(IFN)- , and tumor necrosis factor (TNF)- on the culture medium to investigate the effects
of ginsenoside Rb1. Results : Compared with C6 glioma cells treated with LPS/IFN- /TNF- ,
C6 glioma cells treated with LPS/IFN- /TNF- /ginsenoside Rb1 showed marked increase in
the NO production and apoptosis. Ginsenoside Rb1 induces the NO production in C6 glioma
cells in dose-dependent manner. When C6 glioma cells treated with LPS/IFN- /TNF- /ginsenoside
Rb1 were incubated with the specific inhibitor of iNOS, S-Methyl-2-thiopseudoureasulfate
(SMT), both NO production and apoptosis in C6 glioma cells was significantly decreased.
Ginsenoside Rb1 induced the expression of iNOS mRNA and iNOS protein in C6 glioma cells.
Conclusions : These results suggest that the induction of iNOS expression and subsequent

참고문헌 (Reference)

1 "influenceon neurotransmitter uptake in rat brain synaptosomes" 3 : 221-4, 1985

2 "Trial of a new medium-term model usingbenzo pyrene induced lung tumor in newborn mice" 15 : 839-45, 1995

3 "Transcriptional activation of the Cu Zn-superoxide dismutase gene through the AP2 site by ginsenosideRb2 extracted from a medicinal plant" 271 : 24539-43, 1996

4 "Protective effectof ginsenosides,active ingredients of Panax ginseng on kainic acidinducedneurotoxicity in rat hippocampus" 325 : 129-33, 2002

5 "Protective effectof ginsenoside Rg1 on dopamine-induced apoptosis in PC12 cells" 22 : 673-8, 2001

6 "Protection of ischemic hippocampalneurons by ginsenoside Rb1 a main ingredient of ginseng root" 28 : 191-200, 1997

7 "Plant-glycoside modulationof cell surface related to control of differentiation in culturedB16 melanoma cells" 47 : 3863-7, 1987

8 "Panax ginseng pharmacology: a nitric oxide link?" 54 : 1-8, 1997

9 "Neuroprotective effects of ginseng totalsaponin and ginsenosides Rb1 and Rg1 on spinal cord neurons invitro" 173 : 224-34, 2002

10 "Inhibitoryeffects by oral administration of ginsenoside Rh2 on the growth ofhuman ovarian cancer cells in nude mice" 120 : 24-6, 1993

11 "Inhibitory effect of tumormetastasis in mice by saponins,ginsenoside-Rb2 20(R)-and 20(S)-ginsenoside-Rg3, of red ginseng" 18 : 1197-202, 1995

12 "Inhibition of apoptosis by ginsenoside Rg1 in culturedcortical neurons" 110 : 535-9, 1997

13 "Inflammation, free radicals, and antioxidants" 12 : 274-7, 1996

14 "Induction ofapoptosis by a novel intestinal metabolite of ginseng saponin viacytochrome c-mediated activation of caspase-3 protease" 60 : 677-85, 2000

15 "Ginsenosides stimulate endogenous productionof nitric oxide in rat kidney" 28 : 573-80, 1996

16 "Ginsenosides Rb1 and Rg3protect cultured rat cortical cells from glutamate-induced neurodegeneration" 53 : 426-32, 1998

17 "Ginsenoside RH-2 induces apoptoticcell death in rat C6 glioma via a reactive oxygen- and caspase-dependentbut BCL-X(L)-independent pathway" 65 : 33-40, 1999

18 "Ginseng pharmacology: multiple constituentsand multiple actions." 58 : 1685-1693, 1999

19 "Ginseng extract scavenges hydroxylradical and protects unsaturated fatty acids from decompositioncaused by iron-mediated lipid peroxidation" 20 : 145-50, 1996

20 "G1phase-specific suppression of the Cdk2 activity by ginsenoside Rh2in cultured murine cells" 60 : 39-44, 1997

21 "Experimental and epidemiological evidence of the cancerpreventiveeffects of Panax ginseng C.A. Meyer" 54 : 71-81, 1996

22 "Effects of ginsenosides onimpaired performance caused by scopolamine in rats" 312 : 149-51, 1996

23 "Cerebral vasodilationinduced by stimulation of the pterygopalatine ganglion and greaterpetrosal nerve in anesthetized monkeys" 96 : 393-8, 2000

24 "Anti-proliferative effect of ginseng saponinson human prostate cancer cell line" 67 : 1297-306, 2000

25 "Adjuvant effect of ginsengextracts on the immune responses to immunisation against Staphylococcusaureus in dairy cattle" 91 : 29-37, 2003

26 "Activation-induced cell death of rat astrocytes" 900 : 342-7, 2001

27 "Activation of caspase-3protease via a Bcl-2-insensitive pathway during the process of ginsenosideRh2-induced apoptosis" 121 : 73-81, 1997