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항암기전

  • 관리자 (sinbio)
  • 2019-03-13 12:27:00
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암 에  대한 효과


1.특점 암이 아니라 모든 암이 예방되며 흡연자의 암 발생 위험을 감소시킨다.
2.항암 작용 기전
1)혈관신생(Angiogenesis)억제:암세포 주위의 혈관생성을 억제
2)자가소멸(Apoptosis)유도:암 세포 자살 유도
3)분화(Differentiation:종양세포가 정상세포로 쪼개지는 현상)유도
4)돌연변이(Mutation)억제:DNA 손상회복
5)전이(Metastasis)억제: 암세포의 세포 침윤 억제
6)NK(Natural kikller)세포의 활성을 증진
3.방사선 치료 시 건강한 세포의 재생을 돕는다.

1."A case-control study suggests an association (but not necessarily a causal relationship) between use of ginseng and lower cancer rates (n=1987) pairs matched for age, religion, marital status, education, sex, occupation, and smoking status. This study presents the risk of various cancers in relation to ginseng intake based on the data from a case-control study conducted in the Korea Cancer Center Hospital Intakers of fresh ginseng slice, fresh ginseng juice, and white ginseng tea, however, showed no decreasing risk. There was a decrease in risk with the rising frequency and duration of ginseng intake, showing a dose-response relationshipThese findings support the view that ginseng intakers had a decreased risk for most cancers compared with nonintakers." 
사례연구가 1987명의 결혼한 남녀를 대상으로 나이, 지역, 배우자 유무, 교육, 성별, 직업과 흡연상태로 분류되어 행한 사례연구는 인삼의 섭취가  암 발생저하를 시킨다고 생각된다(우연한 관련성이 아니라) 이 연구는 한국의 암 센터병원에서 행한 사례연구로부터 얻어진 인삼섭취와 다양한 암 발생과의 상관관계를 보여 준다
수삼 절편, 수삼 주스나 백삼을 섭취한 사람에게서는 암 발생  위험성이 감소하지 않은 것을 보여준다. 인삼섭취기간과 횟수가 많을수록 위험성은 감소한다(용량 의존적이다)  이들 발견은 인삼의 섭취 자는 비 섭취 자에 비해 대부분의 암 발생 위험성이 줄어든다는 견해를 지지해준다
참고
" 한국의 암 센터에서 행한 연구에 의하면(Yun and Choi 1990)인삼을 많이 복용할수록 암 발생위험이 명백히 감소하며 수삼이나 인삼 쥬스에는 이러한 작용이 없으나 백삼 추출물이나 백삼분말이 가장 효과적 이었다 암 방어 작용은 여자보다는 남자에게서 더 많이 나타났다. 
그 후에 이뤄진 연구에서(Yun and Choi 1995)인삼을 먹은 횟수와 기간에 따라 암 발생위험이 감소하며 처음 복용한 나이에 관계없이 1년 이상 복용한 후 복용기간이 길수록 발생 율은 감소하였다. (홍삼은 0.2,백삼은 0.3, 수삼추출물 0.37은 oddis ratio)를 보였다. 
인삼을 복용하는 흡연자는 비 흡연자에 비해 는 폐나 입술, 후두 ,구강 ,간암의 위험성은 줄었으나 대장, 결장 암, 위암이나 식도암의 발생은 줄이지 못했다. 
2.Surveys have been taken on the relationship of Ginseng usage to the risk of cancer. Reports have concluded that Ginseng may improve resistance to contracting this illness. Studies with animals have shown anti-proliferative effects on human renal cancer anticarcinogenic, augmentation of NK activity, and the generation of LAK cells from both NK and T cells through endogenously produced multiple cytokines.This property may contribute to its effectiveness in the immunoprevention and immunotherapy of cancer."  
인삼과 암 발생 위험성과의 상관관계를 조사하였다. 인삼이 암에 걸리는 것에 대한  저항성을 증강시킨다고 결론지었다. 동물연구는 인간의 신장 암에서 항 증식효과와 항 발암작용,NK활성증가 및 NK와 T세포로부터 LAK세포의 생산(내인 성으로 생성되는 다양한 면역단백을 통하여)을 보여주었다 이 성질은 암의 면역학적 치료와 면역방어에 효과적으로 기여할 것으로 생각된다.

  
          문헌 
1.Mutat Res. 2003 Feb-Mar;523-524:63-74.
Experimental and epidemiological evidence on non-organ specific cancer preventive effect of Korean ginseng and identification of active compounds.
Yun TK.
Laboratory of Experimental Pathology, Korea Cancer Center Hospital, 215-4 Gongneung Dong, Nowon Ku, Seoul 139-706, South Korea. tkyun@ nuri.net
Panax ginseng C.A. Meyer has been the most highly recognized medicinal herb in the Orient. The prolonged administration of red ginseng extract significantly inhibits the incidence of hepatoma and also proliferation of pulmonary tumors induced by aflatoxin B(1) and urethane. Statistically significant anticarcinogenic effects were in aged or heat treated extracts of ginseng and red ginseng made by steaming in a 9 weeks medium-term anticarcinogenicity test using benzo[a]pyrene. In case-control studies, odds ratios (OR) of the cancer of lip, oral cavity and pharynx, larynx, lung, esophagus, stomach, liver, pancreas, ovary, and colorectum were significantly reduced. As to the type of ginseng, the ORs for cancer were reduced in user of fresh ginseng extract intakers, white ginseng extract, white ginseng powder, and red ginseng. In a cohort study with 5 years follow-up conducted in a ginseng cultivation area, ginseng users had a decreased relative risk (RR) compared with non-users. The relative risks (RRs) of ginseng users were decreased in gastric cancer and lung cancer. These findings strongly suggest that Panax ginseng C.A. Meyer cultivated in Korea has non-organ specific cancer preventive effects against various cancers. To investigate the active components for cancer prevention, several fractions of fresh and red ginseng and four semi-synthetic ginsenoside Rh(1), Rh(2), Rg(3) and Rg(5), the major saponin components in red ginseng, were prepared among the ginsenosides. By using Yun's model, Rg(3) and Rg(5) showed statistically significant reduction of lung tumor incidence and Rh(2) had a tendency to decrease the incidence. In conclusion, these results strongly suggested that Panax ginseng C.A. Meyer cultivated in Korea is a non-organ specific cancer preventive against human cancers and also indicated that the anticarcinogenicity or human cancer preventive effect of Panax ginseng is due to ginsenoside Rg(3), Rg(5) and Rh(2).
PMID: 12628504 [PubMed - indexed for MEDLINE] 


2.Phytother Res. 2005 Jan;19(1):65-71
Evaluation of chemopreventive action and antimutagenic effect of the standardized Panax ginseng extract, EFLA400, in Swiss albino mice.
? Panwar M, Kumar M, Samarth R, Kumar A. 
Radiation and Cancer Biology Laboratory, Department of Zoology, University of Rajasthan, Jaipur 302 004, India.
In the present investigation the chemopreventive action and antimutagenic effects of a standardized Panax Ginseng extract (EFLA400, processed Panax ginseng extract containing a high titre of ginsenoside Rg3 (>3.0% w/w) known as Phoenix ginseng) in Swiss albino mice have been evaluated. The oral administration of EFLA400 at 1, 3 and 10 mg/kg body weight at pre, peri and post-initiational phases, showed significant reductions in the number, size and weight of the papillomas. A significant reduction in tumour incidence (71.41 +/- 6.73%, 72.19 +/- 4.54% and72.19 +/- 4.54% at 1, 3 and 10 mg/kg body weight, respectively) was observed in animals in the EFLA400 treated group compared with 100% tumour incidence in the control group. The cumulative number of papillomas during an observation period of 16 weeks was significantly reduced in the EFLA400 treated group (24 +/- 0.94, 16 +/- 1.41 and 11 +/- 1.41 at 1, 3 and 10 mg/kg body weight, respectively). However, the average latent period was significantly increased from 10.81 +/- 0.1 weeks in the control group to 12.39 +/- 0.28 weeks in the treated group (10 mg/kg body weight). The average tumour weight was recorded as 128.55 +/- 8.48, 116.00 +/- 8.48 and 57.5 +/- 3.29 mg in 1, 3 and 10 mg/kg body weight EFLA400 treated groups respectively. Chromosomal aberrations and micronuclei induction was also evaluated in bone marrow cells. These genotoxicity end-points were compared with papilloma occurrence at the same dose levels of carcinogen and ginseng. In the EFLA400 treated groups significantly reduced frequencies of chromosomal aberrations and micronuclei induced by DMBA and croton oil were observed. However, the maximum decrease in the frequencies of chromosomal aberrations and micronuclei were recorded in the 10 mg/kg body weight EFLA400 treated group than that of the 1 and 3 mg/kg body weight EFLA400 treated animals. The results from the present study suggest the dose dependent effectiveness of EFLA400 in chemoprevention and antimutagenicity in Swiss albino mice. 
Copyright (c) 2005 John Wiley & Sons, Ltd.
PMID: 15799001 [PubMed - indexed for MEDLINE]
표준화된 고려인삼 추출물(EFLA400)의 화학적 예방과 항전이 효과의 평가
이번연구에서는 표준화된 고려인삼(Phoenix인삼으로 알려진 고려인삼 가공 추출물로서 Rg3가 3.0%w/w이상포함됨:EFLA400)의 항 전이와 화학적 예방 효과를 Swiss albino 생쥐에서 평가하였다.EFLA400을 1,3,10mg/kg전 주변(peri),후로 경구로 투여한 것은 padben종의 무게 숫자 크기를 의미 있게 감소시켰다. 대조군에서 100%의 종양이 발생 한 것과 비교하여 EFLA400으로 처리 한 군에서는 종양 발생이 1mg에서 71.41 +/- 6.73%,3mg에서 72.19 +/- 4.54%,10mg에서72.19 +/- 4.54%f로 의미 있는 감소가 있었다. 그러나 평균 잠복기는 대조군  10.81 +/- 0.1에서 12.39 +/- 0.28 (10mg/kg) 주로 의미 있게 증가하였다.EFLA400으로 처치한 군에서 평균 종양 무게는 128.55 +/- 8.48/1mg,116.00 +/- 8.48 3mg,57.5 +/- 3.29 mg/10mg/kg으로 기록되었다. 크로모솜 이탈과 소핵 유도는 골수 세포에서 평가되었다. 이들 유전 독성 종말점은 같은 농도의 발암물질과 인삼에서 유두종의 발생으로 비교되었다.EFLA400으로 처치한 군은 DMBA와 croton oil로 유도된  크로모솜 이탈과 소액의 빈도를 의미 있게 감소시켰다. 그러나 최대 감소는 1mg,3mg보다는 10mg으로 처리한 군에서 기록되었다. 이번 연구 결과는 Swiss albino에서 EFLA400의  화학적 예방과 항 전이의 효과가 용량의존적임을 추측 하게 한다.


3 Biochem Pharmacol. 2006 Aug 14;72(4):437-45. Epub 2006 May 12.
The angiosuppressive effects of 20(R)- ginsenoside Rg(3).

? Yue PY, Wong DY, Wu PK, Leung PY, Mak NK, Yeung HW,Liu L, Cai Z, Jiang ZH,Fan TP, Wong RN. 

Hung Lai Ching Laboratory of Biomedical Science, Research and Development Division, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong.

Aberrant angiogenesis is an essential step for the progression of solid tumors. Thus anti-angiogenic therapy is one of the most promising approaches to control tumor growth. In this study, we examined the ability of 20(R)-ginsenoside Rg(3) (Rg(3)), one of the active compounds present in ginseng root, to interfere with the various steps of angiogenesis. Rg(3) was found to inhibit the proliferation of human umbilical vein endothelial cells (HUVEC) with an IC(50) of 10nM in Trypan blue exclusion assay. Rg(3) (1-10(3)nM) also dose dependently suppressed the capillary tube formation of HUVEC on the Matrigel in the presence or absence of 20ng/ml vascular endothelial growth factor (VEGF). The VEGF-induced chemoinvasion of HUVEC and ex vivo microvascular sprouting in rat aortic ring assay were both significantly attenuated by Rg(3). In addition, Rg(3) (150 and 600nM) remarkably abolished the basic fibroblast growth factor (bFGF)-induced angiogenesis in an in vivo Matrigel plug assay. The Matrix metalloproteinases (MMPs), such as MMP-2 and MMP-9, which play an important role in the degradation of basement membrane in angiogenesis and tumor metastasis present in the culture supernatant of Rg(3)-treated aortic ring culture were found to decrease in their gelatinolytic activities. Taken together, these data underpin the anti-tumor property of Rg(3) through its angiosuppressive activity.
PMID: 16793023 [PubMed - in process]
20(R)-Rg3의 혈관 억제효과
異常적인 혈관신생은 고착 종약의 진행에 필수적인 과정이다. 따라서 항 혈관신생 치료는 종양의 성장을 조절하는데 가장 중요한 약정된 접근의 하나이다.
이 연구에서 인삼의 활성 성분위 하나인  20(R)-Rg3(Rg3)가 혈관신생의 다양한 과정에 작용 능력을 실험하였다.Rg3는 인간 배꼽 주위 정맥 상피세포(HUVEC0의 증식을 IC(50) 10nM농도에서 억제하였다(Trypan blue exclusion assay.).
Rg(3) (1-10(3)nM)역시 Matrigel에서  HUVEC의 모세관 형성을 용량 의존적으로 억제하였다(20ng/ml의 혈관 상피성장인자(VEGF)가 있거나 없거나).  VEGF로 유도된 HUVEC의 화학물 침윤과  쥐의 동맥에서 생체 내 모세혈관의 싹 분석은 모두 의미 있게 감소하였다. 나아가Rg3 (150 and 600nM)은  기초적인  섬유아세포 성장인자(bFGF)로 유도된 혈관신생을 현저하게 상쇄시켰다(생체 내 Matrigel plug assay).Rg3로 처리한 동맥 배양의 배양 상청 액에서 종양 전이와 혈관신생의 기저 세포막의 퇴화에 중요역할을 하는 MMP-2나 MMP-9같은 Matrix metalloproteinases (MMPs)의 젤라틴양 작용이 감소하는 것이 발견되었다.일괄해서 이들 데이터는 Rg3가 혈관억제작용을 통하여 항 종양작용을 지지한다.

4. Basic Clin Pharmacol Toxicol. 2006 Jun;98(6):588-92.
2.Ginsenoside 20(S)-protopanaxadiol inhibits the proliferation and invasion of human fibrosarcoma HT1080 cells.
? Li G, Wang Z, Sun Y, Liu K, Wang Z. 

School of Life Sciences, Lanzhou University, Lanzhou, People's Republic of China.

Ginsenoside 20(S)-protopanaxadiol, one of metabolites of ginseng saponins, has been well characterized to possess the pleiotropic anticancer capabilities in several cancer cell lines. The object of this study was to investigate the effects of ginsenoside 20(S)-protopanaxadiol on the invasion in vitro and the expression of matrix metalloproteinase-2 in human fibrosarcoma HT1080 cells in absence of cytotoxicity. Our results showed that ginsenoside 20(S)-protopanaxadiol exerted a concentration-dependent inhibitory effect on the proliferation of HT1080 cells (IC50 was 76.78+/-2.24 microM, 48 hr). Treatment with 20(S)-protopanaxadiol significantly declined the invasive capacity of HT1080 cells compared to the control cells (P<0.01) in the in vitro invasion assay. Further analysis with gelatin zymography and western blotting revealed that both the activity and the expression of matrix metalloproteinase-2 decreased dramatically in a concentration-dependent manner (P<0.01). Taken together, these results indicated that ginsenoside 20(S)-protopanaxadiol is able to inhibit the invasiveness of HT1080 cells significantly in vitro and this action may be primarily due to down-regulating the expression of matrix metalloproteinase-2. Ginsenoside 20(S)-protopanaxadiol, a metabolite of ginseng, may be applied as a potential therapeutic agent in the prevention and treatment of cancer.
PMID: 16700822 [PubMed - in process]
 20(S)-PPD은  인간 섬유육종 HT1080세포의 증식과 침윤을 억제 한다
20(S)-PPD은 몇 종의 암세포에서 다면적인 항암 능력을 지닌 특징이 있다.
이연구의 목적은 20(S)-PPD가 실험관내 실험에서 침윤 및 인간 섬유 육종 HT1080세포에서 세포독성 없이 matrix metalloproteinase-2 의 출현에 대한 효과를 연구하기 위해서이다.
결과는 20(S)-PPD 농도 비례적으로 HT1080세포의 증식을 억제하는 효과를 보여주었고((IC50 was 76.78+/-2.24 microM, 48 hr) 실험관 내 실험을 통한 침윤 분석에서 대조군에 비해 HT1080세포의 침윤 력을 의미 있게 감소시켰다. 젤라틴 zymography and western blotting을 통한 분석은 농도 의존적으로 matrix metalloproteinase-2 의 출현과 작용D 감소하는 것을 보여준다. 일괄해서 이들 결과는 20(S)-PPD 는 실험관 내 TFGJA에서 HT1080 세포의 침윤을 의미 있게 억제하는데 이는 matrix metalloproteinase-2의 출현을 감소방향으로 조절하는데 기인하는 것 같다.
20(S)-PPD 은  암의 치료와 예방에 충분한 치료적 물질로 응용될 수 있다
5. Basic Clin Pharmacol Toxicol. 2006 Apr;98(4):411-5.
Ginsenoside Rh(2) enhances antitumour activity and decreases genotoxic effect of cyclophosphamide.
? Wang Z, Zheng Q, Liu K, Li G, Zheng R. 
School of Life Sciences, Lanzhou University, Lanzhou, People's Republic of China.

Ginsenoside Rh(2), a panaxadiol saponins, possesses various antitumour properties. Cyclophosphamide, an alkylating agent, has been shown to possess various genotoxic and carcinogenic effects, however, it is still used extensively as an antitumour agent and immunosuppressant in the clinic. Previous reports reveal that cyclophosphamide is involved in some secondary neoplasms. In this study, the antitumour activity and genotoxic effect of oral intake of ginsenoside Rh(2) combined with intraperitoneal injection of cyclophosphamide was investigated. Meanwhile, C57BL/6 mice bearing B16 melanoma and Lewis lung carcinoma cells were respectively used to estimate the antitumour activity in vivo. The clastogenic activity in bone marrow polychromatic erythrocytes was assayed by frequency of micronucleus. The DNA damage in peripheral white blood cells was assayed by single cell gel electrophoresis as well. The results indicated that oral administration of Rh(2) (5, 10 and 20 mg/kg body weight) alone has no obvious antitumour activity and genotoxic effect in mice, while Rh(2) synergistically enhanced the antitumour activity of cyclophosphamide (40 mg/kg body weight) in a dose-dependent manner. Rh(2) decreased the micronucleus formation in polychromatic erythrocytes and DNA strand breaks in white blood cells in a dose-dependent way. Our results suggest that ginsenoside Rh(2) is able to enhance the antitumour activity and decrease the genotoxic effect of cyclophosphamide.
PMID: 16623867 [PubMed - in process]
Rh2는  cyclophosphamide의 항암작용을 향상하고 유전 독성을 감소시킨다.
Rh2는 ppd계 사포닌으로 다양한 항암 성질을 지녔다.Cyclophosphamide는 alkylating제로 다양한 유전독성과 항암 효과를 지닌 것으로 보이며 항암제로 면역억제제로 임상적으로 아직도 많이 사용된다. 이전 연구에서는 cyclophosphamide 가 어떤 이차 신생 물에 포함된 것을 보여주었다. 이번연구에서는  cyclophosphamide를 복강 내 주사로 투여하고 같이   Rh2의 경구 투여에 의한 항 암 작용과 유전 독성 효과를 연구하였다.  B16 흑생종과 폐 암을 지닌 C57BL/6 생쥐를 대상으로 항 암 작용을 평가하였다(생체 내 실험). 골수 다 염성 조혈모세포에서 clastogenic 작용은  소핵의 주파수에 의해 분석하였다. 말초 백혈구의 DAN 손상은 단세포 겔 전기 이동 법에 의해 분석하였다. 결과는 Rh2 만의 경구투여(5,10,20mg/kg 체중)sms  생쥐에서 명백한 항암작용과 유전독성이 없는 반면 Rh2는 용량 의존적으로cyclophosphamide940mg/kg체중)의 항암작용을 상승적으로 향상시키는 것을 보여준다.
Rh2는  백혈구에서 용량 의존적으로 다 염 조혈 모세포와 DNA 나선에서 소핵 형성을 감소시켰다.  이들 결과는 Rh2는 cyclophosphamide의 유전 독성을 감소시키고 항 암 작용을 향상시키는 것으로 보인다 

6. Can J Physiol Pharmacol. 2004 Jul;82(7):431-7
Rh2, a compound extracted from ginseng, hypersensitizes multidrug-resistant tumor cells to chemotherapy.

? Jia WW, Bu X, Philips D, Yan H, Liu G, Chen X, Bush JA, Li G. 

Department of Surgery, University of British Columbia, Vancouver, Canada. wjia@interchange.bc.ca

Rh2 is a ginsenoside extracted from ginseng that has drawn attention in a few laboratories in Asian countries because of its potential tumor-inhibitory effect. In the present study, we tested Rh2 on many tumor-cell lines for its effects on cell proliferation, induction of apoptosis, and potential interaction with conventional chemotherapy agents. Our results showed that Rh2 inhibited cell growth by G1 arrest at low concentrations and induced apoptosis at high concentrations in a variety of tumor-cell lines, possibly through activation of caspases. The growth arrest and apoptosis may be mediated by 2 separate mechanisms. Apoptosis is not dependent on expression of the wild-type p53 nor the caspase 3. In addition, the apoptosis induced by Rh2 was mediated through glucocorticoid receptors. Most interestingly, Rh2 can act either additively or synergistically with chemotherapy drugs on cancer cells. Particularly, it hypersensitized multidrug-resistant breast cancer cells to paclitaxel. These results suggest that Rh2 possesses strong tumor-inhibiting properties, and potentially can be used in treatments for multidrug-resistant cancers, especially when it is used in combination with conventional chemotherapy agents.
PMID: 15389289 [PubMed - indexed for MEDLINE]
인삼에서  추출한 Rh2는  다 제 내성 종양세포를 화학요법 제에  고 민감 하게 한다
Rh2는 아시아의 몇몇 실험에서 잠재적인 종양 억제 효과로 주목 받은 인삼으로부터 추출된 진세노사이드이다
이번연구에서 우리는 Rh2의 많은 종양세포 라인에 대한 세포 증식, 자가 소멸 유도와  기존의 화학요법제와 잠재적인 상호작용을 실험하였다. 결과는 다양한 종양 세포라인에서 아마도 caspases의 활성을 통하여  Rh2가 저 농도에서  G1 억제에 의해 세포 성장을 억제하고 고 농도에서 세포 자가 소멸을 유도하는 것을 보여 준다. 성장 억제와 세포 자가 소멸은 2개의 분리된 기전에 의해 매개된 것이다. 세포 자가 소멸은 넒은 형태 p53이나 caspase3의 출현에 의존 한 것은 아니다. 나아가 Rh2로 유도된 세포 자가 소멸은 글루코코르티코이드 수용체를 통해 매개되었다. 가장 흥미롭게도 Rh2는 암세포에 화학요법제와 상가 또는 상승으로 작용 할 수 있다는 것이다. 특히  다 제 내성 유방암 세포를 paclitaxel에 고 민감하게 하였다. 이들 결과는 Rh2는 강력한 종양 억제 성질을 지녔으며 기존의 화학요법제와 병용하여 사용 시 다 제 내성 암의 치료에 잠재적으로 사용될 수 있을 것이다.
7.Cancer Lett. 2000 Apr 28;152(1):97-106.
Preventive effect of epicatechin and ginsenoside Rb(2) on the inhibition of gap junctional intercellular communication by TPA and H(2)O(2).
Kang KS, Kang BC, Lee BJ, Che JH, Li GX, Trosko JE, Lee YS.
Department of Veterinary Public Health, College of Veterinary Medicine, Seoul National University, 103 Seodun-Dong, Kwonsun-Ku, Suwon, South Korea
The anticarcinogenic effects of epicatechin (EC) and ginsenoside Rb(2) (Rb(2)), which are major components of green tea and Korea ginseng, respectively, were investigated using a model system of gap junctional intercellular communication (GJIC) in WB-F344 rat liver epithelial cells. 12-O-tetradecanoylphorbol-13-acetate (TPA) and hydrogen peroxide, known as cancer promoters, inhibited GJIC in the epithelial cells as determined by the scrape loading/dye transfer assay, fluorescence redistribution assay after photobleaching, and immunofluorescent staining of connexin 43 using a laser confocal microscope. The inhibition of GJIC by TPA and H(2)O(2) was prevented with treatment of Rb(2) or EC. The effect of EC on GJIC was stronger in TPA-treated cells than in H(2)O(2)-treated cells, while the effect of Rb(2) was opposite to that of EC. EC, atthe concentration of 27.8 microg/ml, prevented the TPA-induced GJIC inhibition by about 60%. Rb(2,) at the concentration of 277 microg/ml, recovered the H(2)O(2)-induced GJIC inhibition by about 60%. These results suggest that Rb(2) and EC may prevent human cancers by preventing the down-regulation of GJIC during the cancer promotion phase and that the anticancer effect of green tea and Korea ginseng may come from the major respective components, EC and Rb(2).PMID: 10754211[PubMed - indexed for MEDLIN
8.Planta Med. 2001 Apr;67(3):213-8.
In vitro inhibitory effect of protopanaxadiol ginsenosides on tumor necrosis factor (TNF)-alpha production and its modulation by known TNF-alpha antagonists.
Cho JY, Yoo ES, Baik KU, Park MH, Han BH.Department of Immunopharmacology, R & D Center, Daewoong Pharmaceutical Co, Sungnam, Korea. jae.cho@ucl.ac.uk
Ginsenosides are the major principles of Panax ginseng C. A. Meyer (Araliaceae) used as a mild oriental folk medicine. In this report, we have examined the inhibitory potency of protopanaxadiol ginsenosides (PPDGs) such as Rb1, Rb2 and Rc, and their co-treatment effect with known tumor necrosis factor (TNF)-alpha antagonists on TNF-alpha production in either murine (RAW264.7) or human (U937) macrophages stimulated with lipopolysaccharide (LPS). Rb1, and Rb2 strongly suppressed TNF-alpha production in RAW264.7 cells with an IC50 of 56.5 and 27.5 microM, respectively, and in differentiated U937 cells with an IC50 of 51.3, and 26.8 microM, respectively. The inhibitory activity of Rb1 and Rb2 was significantly increased by pharmacological agents against protein kinase C, protein tyrosine kinase, and protein kinase A, and anti-rheumatoid arthritis drugs, such as chloroquine and steroid drugs. In contrast, only cyclic AMP phosphodiesterase (cAMP PDE) inhibitors among cAMP-elevating agents did not change the inhibitory potency of PPDGs. These data suggest that PPDGs may possess potential therapeutic efficacy against TNF-alpha mediated disease and the therapeutic potency of PPDGs may be enhanced when co-treated with various kinds of known TNF-alpha antagonists but not with cAMP PDE inhibitors.PMID: 11345690 [PubMed - indexed for MEDLIN

9.Biochem Biophys Res Commun. 1998 May 29;246(3):725-3
An intestinal bacterial metabolite of ginseng protopanaxadiol saponins has the ability to induce apoptosis in tumor cells.
Wakabayashi C, Murakami K, Hasegawa H, Murata J, Saiki I.Department of Pathogenic Biochemistry, Research Institute for Wakan-Yaku, Toyama Medical and Pharmaceutical University, Toyama, Japan.
Our previous study demonstrated that the in vivo anti-metastatic effect induced by oral administration of ginseng protopanaxadiol saponins was mediated by their metabolic component M1, and that the growth, invasion and migration of tumor cells were inhibited by M1 but not by ginsenosides. Here we investigated the inhibitory mechanism of M1 on the growth of tumor cells. M1 inhibited the proliferation of B16-BL6 mouse melanoma cells in a time- and dose-dependent manner, with accompanying morphological changes at the concentration of 20 microM. In addition, at 40 microM M1 induced apoptotic cell death within 24 h. Fluorescence microscopy revealed that dansyl M1 entered the cytosol and quickly reached the nuclei (approximately 15 min). Western blot analysis revealed that M1 rapidly up-regulated the expression of p27Kip1, but down-regulated the expression of c-Myc and cyclin D1 in a time-dependent manner. Thus, the regulation of apoptosis-related proteins by M1 is responsible for the induction of apoptotic cell death, and this probably leads to the anti-metastatic activity in vivo.PMID: 9618279 [PubMed - indexed for MEDLINE] 
세포자사소멸과 관련된 단백질을 조절하여 M1(Compound k)는 세포 자가 소멸을 유도하며 이는 생체 내에서 항 전이작용으로 아마도 나타날 것이다
10.Carcinogenesis. 2004 Oct 21; [Epub ahead of print]
Anti-tumor promotional effects of a novel intestinal bacterial metabolite (IH-901) derived from the protopanaxadiol type ginsenosides in mouse skin.
Lee JY, Shin JW, Chun KS, Park KK, Chung WY, Bang YJ, Sung JH, Surh YJ.National Research Laboratory of Molecular Carcinogenesis and Chemoprevention, College of Pharmacy, Seoul National University, Seoul 151-742, Korea.
Epidemiological studies have demonstrated that ginseng intake decreases the risk of cancer. Ginseng saponins (ginsenosides) have been regarded as principal components responsible for the majority of pharmacological activities exerted by ginseng. IH-901 [20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol], an intestinal bacterial metabolite derived from protopanaxadiol type saponins of Panax ginseng C.A. Meyer, has been reported to possess anti-tumor effects, including inhibition of invasion, metastasis and angiogenesis and induction of tumor cell apoptosis. Tumor promotion often accompanies an elevated ornithine decarboxylase (ODC) activity, acute inflammation, and induction of cyclooxygenase-2 (COX-2) activity. Here we examined the effects of IH-901 on tumor promotion and related molecular events in mouse skin in vivo. IH-901 pretreatment inhibited ear edema induced by the prototype tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in a female ICR mice. Topical application of IH-901 onto shaven backs of female ICR mice led to inhibition of TPA-induced expression of COX-2 and production of prostaglandin E2. The eukaryotic transcription factor NF-kappaB has been involved in intracellular signaling pathways associated with inflammation and carcinogenesis. IH-901 attenuated TPA-induced epidermal NF-kappaB DNA binding in mouse skin which appeared to be mediated by blocking phosphorylation and subsequent degradation of IkappaBalpha. In an attempt to elucidate the molecular mechanisms by which IH-901 inactivates NF-kappaB, its effects on activation of upstream signaling kinases were explored. IH-901 treatment mitigated the activation of ERK1/2 and Akt signaling. In another experiment, topically applied IH-901 suppressed the activity as well as expression of ODC in a dose-dependent fashion. In addition, IH-901 given prior to each topical dose of TPA markedly lowered the number of papillomas in mouse skin induced by 7,12-dimethylbenz[a]anthracene. Taken together, these findings suggest that IH-901 exerts anti-inflammatory effects by inhibiting TPA-induced COX-2 expression, which may contribute to itsanti-tumor promoting effects on mouse skin carcinogenesis.PMID: 15498788 [PubMed - as supplied by publishe
11.Cancer Res. 1995 Mar 15;55(6):1221-3.
Suppression of the formation of sister chromatidexchanges by low concentrations of ginsenoside Rh2 in human blood lymphocytes.
Zhu JH, Takeshita T, Kitagawa I, Morimoto K.Department of Hygiene and Preventive Medicine, Osaka University School of Medicine, Japan.
To assess the antimutagenic potentials of ginsenoside Rh2 (Rh2), its effects on the baseline and mitomycin C-induced sister chromatid exchange (SCE) were examined in human peripheral blood lymphocytes (PBLs). The SCE frequency in PBLs treated with various concentrations of Rh2 for 72 h was decreased in a dose-dependent manner and was significantly lower than the baseline levels at 1.0 x 10(-10) M and 1.0 x 10(-7) M. The SCE frequency in PBLs treated with both Rh2 and mitomycin C was significantly (P < 0.001) less than that in PBLs treated with only mitomycin C. Cell cycle kinetics, as indicated by the proliferation and mitotic indices, was not significantly affected by Rh2 of various concentrations in the PBLs throughout the present experiments. This is the first report which showed convincingly a reduction of SCE in normal human cells. The mechanism remains to be elucidated in future studies.PMID: 7882311 
[PubMed - indexed for MEDLINE]
Rh2의 항 변이유발능력을 평가하기 위해 인간 모세혈관의 임파구(PBL) 에 mitomycin으로 유도 된 chromatid 계수의 변화(SCE)에 대한 효과를 시험 했다.에 SCE의 빈도는 Rh2를 적용한 농도(1.0*10-10M)과 1.0*10-7M)에서 용량 의존적으로 감소하였고 기준치보다 의미 있게 낮았다.Rh2와 mytomycinC를 같이 적용한 경우에는 mytomycin단독 적용 시 보다 의미 있게 낮았다. 증식을 의미하는 세포주기 운동은 농도에 관계없이 의미 있게 영향을 받지 않았다 인간의 세포에 있는 SCE의 감소를 분명하게 보여주는 첫 번째 보고서이며 앞으로의 연구와 평가가 남아있다
12. Life Sci. 1999;65(3):PL33-4
Ginsenoside RH-2 induces apoptotic cell death in rat C6 glioma via a reactive oxygen- and caspase-dependent but Bcl-X(L)-independent Pathway
Kim HE, Oh JH, Lee SK, Oh YJ.Department of Biology, Yonsei University College of Science, Seoul, Korea.
We used the rat C6 gliomal cell line to investigate the potential role of ginsenoside Rh2 (G-Rh2) in brain tumor. G-Rh2 induced many apoptotic manifestations in C6 gliomal cells as evidenced by changes in cell morphology, generation of DNA fragmentation, activation of caspase and production of reactive oxygen species (ROS). As a result, cotreatment with antioxidants or a broad-spectrum caspase inhibitor, N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone effectively attenuated G-Rh2-induced cell death. However, specific cleavage of poly(ADP-ribose)polymerase into 85 kDa protein was not detected as demonstrated in many other apoptotic paradigms. Expression levels of Bcl-2 and Bax remained unchanged following G-Rh2 treatment. Furthermore, G-Rh2-induced cell death inC6 gliomal cells overexpressing antiapoptotic protein, Bcl-X(L), was comparable to that in parental cells. Taken together, our data indicate that G-Rh2-induced cell death is mediated by the generated ROS and the activation of caspase pathway in a Bcl-X(L)-independent manner.
PMID: 10447219 [PubMed - indexed for MEDLINE]
쥐의 C6신경교종을 뇌 암에 대한 Rh2의 능력을 연구하기 위해 사용하였다.Rh2는 세포 형태학적인 변화,DNA 분열의 생성과 반응적 인산소종(ROS)의 생산과 caspase활성 등을 통하여 C6신경 교종에서 많은 수의 세포자가소멸을 명백하게 유도하였다. 항산화제나 광범위 caspase저해제를 같이 사용한 결과 N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone은 효과적으로 감소하였다
13.Yao Xue Xue Bao. 1996;31(10):742-5.
[Differentiation of B16 melanoma cells induced by ginsenoside RH2]
[Article in Chinese]Xia LJ, Han R.Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing.
The effect of ginsenoside Rh2, a constituent isolated from Panax ginseng C. A. Meyer, on the growth of tumor cells in vitro was investigated. The results showed that Rh2 inhibited the growth of B16 cells at the concentration of 10 micrograms.ml-1 (IC50: 4.1 micrograms.ml-1). Rh2 was found to significantly induce the activity of differentiation of B16 cells at the concentration of 10 micrograms.ml-1 in vitro. The melanin synthesis of Rh2 in treated B16 cells was increased. Morphologically, the Rh2 induced B16 cells turned to be epithelioid (상피모양의)cells. B16 cells became dendrite(수지상돌기) shaped morphologically at higher concentration of Rh2. Flow cytometry demonstrated that the B16 cells treated with Rh2 were blocked at G1 phase.PMID: 9863241 [PubMed - indexed for MEDLIN

 

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