1.Zhongguo Zhong Yao Za Zhi. 2005 Oct;30(20):1617-21.Links
[Effects of ginsenoside Rh2(GS-Rh2) on cell cycle of Eca-109 esophageal carcinoma cell line]
[Article in Chinese]
Department of Pathology, Hebei Medical University, Shijiazhuang 050017, China.
OBJECTIVE: To investigate the effects of ginsenoside Rh2 (GS-Rh2) on growth inhibition and cell cycle of Eca-109 esophageal carcinoma cell line in culture. METHOD: The effects of GS-Rh2 on cell growth inhibition was detected by MTT assay. Cell cycle was analyzed by flow cytometry (FCM). Cell morphology was observed by a light microscope after HE staining. The protein expression of cell cycle components (cyclinE, CDK2, p21WAF1) were examined by immunocytochemistry and Western blot. The mRNA expression were examined by semiquantitative RT-PCR. RESULT: GS-Rh2 inhibited the proliferation of Eca-109 cells in dose and time-dependent manners. The inhibition rate was about 50% after 1-day treatment with 20 microg x mL(-1) GS-Rh2 x 20 microg x mL(-1) GS-Rh2 induced the mature differentiation and morphological reversion. With increasing dose of GS-Rh2 treatment, the cell number of G0/G1 phase was increased, whereas it decreased at S and G2/M phase. There was significant difference between 10, 20 microg x mL(-1) GS-Rh2 groups and the corresponding group without GS-Rh2 treatement. After treating cells by 20 microg x mL(-1) GS-Rh2 for 1, 2, 3 days individually, the protein and mRNA expression of both cyclinE and CDK2 reduced, while the expression of p21WAF1 enhanced gradually. CONCLUSION: GS-Rh2 could arrest Eca-109 cells at G0/G1 phase and induce cell differentiation tending to normal. Furthermore, GS-Rh2 had an effect on expression of cell cycle components (cyclinE, CDK2 and p21WAF1) to inhibit Eca-109 cell proliferation.
PMID: 16422547 [PubMed - in process]
Eca-109 식도 암 세포의 세포 순환에 대한 Rh2의 효과
목적: 배양된 Eca-109 식도 암 세포의 세포 순환과 성장 억제에 대한 Rh2의 효과를 연구하기 위함
방법: 성장 억제 효과는 MTT로 분석 하였다.세포 주기는 FCM으로 분석하였다. 세포 형태는 HE로 염색 후 광 현미경으로 관찰하였다. 세포 순환의 단백질 출현은(cyclinE, CDK2, p21WAF1) Western blot와 면역세포화학적으로 검사하였다.mRNA 출현은 semi 정량적 RT-PCR로 검사 하였다.
결과:Rh2는 용량과 시간 의존적으로 Eca-109의 증식을 억제 하였다.억제 율은 하루 동안 20microg/ml로 처리 후 50% 정도였고 성숙 분화와 형태학적 역전을 유도하였다. Rh2 처리를 증가시키면 GO/G1의 세포 숫자는 증가하지만 S와 G2/M에서는 감소하였다. Rh2가 없는 군과 10,20microg/ml군에서는 의미 있는 다른 점이 있었다. 20microg/ml의 Rh2로 각각 1,2,3일 처리한 후 cyclinE와 COX2의 단백질과 mRNA의 출현은 감소한 반면 P21waf1출현은 점차적으로 증가하였다.
결론: Rh2은 Eca-109세포를 GO/GI상에서 억제하고 정상 세포로 세포 분화를 유도한다. 나아가 Eca-109세포 증식을 억제하는 세포 순환 성분(cyclinE, CDK2 and p21WAF1)의 출현에 영향을 미친다.
2.Can J Physiol Pharmacol. 2004 Mar;82(3):183-90
Ginsenosides 20(S)-protopanaxadiol and Rh2 reduce cell proliferation and increase sub-G1 cells in two cultured intestinal cell lines, Int-407 and Caco-2.
? Popovich DG, Kitts DD.
Food, Nutrition and Health, Faculty of Agricultural Science, University of British Columbia, Vancouver, Canada.
Ginsenosides derived from 20(S)-protopanaxatriol (PT) and 20(S)-protopanaxadiol (PD) groups had similar characteristic cytotoxic effects on the growth of two intestinal cells lines, Int-407 and Caco-2. Pure Rh2, a ginsenoside structurally related to PD, inhibited intestinal cell growth at greater than twice the concentration of PD, while Rh1, a ginsenoside structurally related to aglycone PT, had no cytotoxic effect. Concentrations causing growth inhibition of 50% of cells (LC50) for the compounds PD, PT, and Rh2 were 23, 26, and 53 microg/mL, respectively, for Int-407 cells. In comparison, the LC50 for PD and PT was determined to be 24 microg/mL, and that for Rh2 was 55 microg/mL in Caco-2 cells. A standardized North American ginseng extract with a known ginsenosides composition did not induce cytotoxicity in either of the intestinal cell lines. Cell cycle analysis showed characteristically different (P = 0.05) effects of ginsenosides PD, Rh2, and PT in both cell lines. Rh2 treatment of Int-407 caused a significantly (P = 0.05) higher production of sub-G1 (apoptotic) cells (35% +/- 1%) compared with untreated cells (14% +/- 0.3%) after 24 h. PD and Rh2 treatments were both significantly (P < 0.05) higher in apoptotic cells than in untreated cells after 48 and 72 h. Similar results were obtained for treatment of Caco-2 cells. Lactate dehydrogenase (LDH) activity in both cell lines was similar for PD and Rh2 and higher (P = 0.05) than for PT treatment at most time periods. These results show a specific structure-function relationship for bioactive ginsenosides in two contrasting intestinal cell types.
PMID: 15052284 [PubMed - indexed for MEDLINE]
20(s)-PD와 Rh2는 두개의 장 내 세포 라인(Int-407 and Caco-2)에서 세포 증식을 감소시키고 sub-G1을 증가시킨다.
20(S) PT와 PD의 진세노사이드 군은 두개의장 내 세포 라인(Int-407 and Caco-2)의 성장에 유사한 세포독성 특징을 갖는다.순수 Rh2(구조적으로 PD에 속한)은 PD농도보다 2배로 많게 장 내 세포 성장을 억제한 반면 Rh1( 구조적으로PT에 속한) 세포 독성이 없다. Int-407세포에서 50%의 세포(LC50)의 성장 억제를 유발하는 농도는 PD 23,PT 26, Rh2 53microg/mL이었다.Caco-2 세포에서 PD와 PT의 LC50가 24microg/m와 비교하여 Rh2는 55 microg/mL이었다 .알려진 진세노사이드 구성을 지진 표준화된 북미삼은 장 내 세포 라인 양쪽 모두 세포독성을 유도하지 않았다. 세포 순환 분석은 PD,Rh2와 PT의V특징적으로 다른 효과를 보여준다. Int-407를 Rh2로 처리한 것은 비 처치 군에 비해(14%+/-0.3%) 24시간 후 sub-G1(세포 자가 소멸)세포의 의미 있는 높은 생성(35% +/- 1%)을 일으켰다.PD와 Rh2의 처치는 모두 비 처치 군에 비해 48,72시간 후 높은 세포 자가 소멸 세포에서 의미 있게 높았다. 사한 결과가 Caco-2 cells.의 처치에서도 얻어졌다. Lactate dehydrogenase (LDH)작용은 최대 시간에서 PT처리보다 높으면서 PD,Rh2에서 유사하였다. 이들 결과는 두개의 반대적인 장 내 세포 태에서 생활성의 진세노사이드의 구조와 기능의 특별한 관련을 보여주는 것이다.
3. Zhonghua Wai Ke Za Zhi. 2002 Aug;40(8):606-8
[Effect of angiogenesis inhibitor Rg3 on the growth and metastasis of gastric cancer in SCID mice]
[Article in Chinese]Tao H, Yao M, Zou S, Zhao D, Qiu H.Department of Surgery, Zhejiang Provincial People's Hospital, Hangzhou 310014, China.
OBJECTIVE: To study the effect of angiogenesis inhibitor Rg3 on the growth and metastasis of gastric cancer in SCID mice. METHODS: Metastatic model simulating human gastric cancer was established by orthotopic implantation of histologically intact human tumor tissue into the gastric wall of SCID mice. Rg3 was administered by gastric perfusion at doses of 0, 2.5, 5.0, 10.0 mg/kg every day for 6 weeks 1 week after tumor implantation. One week after last administration, the mice were killed and their tumor weight was measured and the presence of metastasis recorded. Intratumoral microvessel density was examined by immunohistochemical staining with anti-CD31 monoclonal antibody. RESULTS: Compared to the untreated controls, the growth of the orthotopically implanted tumor was significantly reduced in weight in mice treated with Rg3 with an inhibition rate of 52.3%, 63.3% and 71.6% at doses of 2.5, 5.0, 10.0 mg/kg, respectively. Tumor metastasis to the liver and peritoneum was also significantly inhibited in a dose-dependent manner. Decreased intratumoral microvessel density was noted in the treated mice. CONCLUSION: Angiogenesis inhibitor Rg3 has strong inhibitory effect on tumor growth and metastasis of human gastric cancer in SCID mice.
PMID: 12417076 [PubMed - indexed for MEDLINE]