• 동의생리병리학회지
• /
• 제20권3호
• /
• pp.690-696
• /
• 2006

Houttuynia cordata Thunb, well known as 'E-Sung-Cho' in Korea, is a traditional medicinal plant generally used in Oriental medicine therapy. In the present study, we investigated the effect of water extract of H. cordafa (WEHC) on the growth of human breast carcinoma MCF-7 cells. Exposure of MCF-7 cells to WEHC resulted in growth inhibition and apoptosis in a dose-dependent manner as measured by MTT assay and fluorescent microscope. The anti-proliferative effect of WEHC was associated with a dose-dependent up-regulation of cyclin-dependent kinase inhibitor p21 in a p53-independent fashion. We found WEHC decreased the levels of cyclooxygenase (COX)-2 and inducible nitric oxide synthease (iNOS) expression without significant changes in the expression of COX-1 , which was correlated with a decrease in prostaglandin $E_2{\;}(PGE_2)$ synthesis. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of H. cordata.

• Archives of Pharmacal Research
• /
• 제23권4호
• /
• pp.338-343
• /
• 2000

The effects of methanol extract of Rubus crategifolius roots and its solvent fractions were investigated on the proliferation of MCF-7 human breast carcinoma cells. The methanol extract inhibited the proliferation of MCF-7 cells in a concentration dependent manner. Moreover, their methanol soluble (W-M) fraction had the greatest inhibitory effect on the growth of MCF-7 cells. To evaluate whether the W-M fraction affects on the cell cycle of MCF-7 cells, cells treated with this fraction were analyzed with flow cytometry. The W-M fraction increased $G_0$/$G_1$phase after 24 h-treatment and induced apoptosis after 48 h-treatment. The hallmark of apoptosis, DNA fragmentation, also appeared by W-M fraction after 48 h-treatment. Furthermore, the methanol extract and its W-M fraction inhibited the activity of the topoisomerase 1 enzyme in the relaxation assay, From these results, their W-M fraction as well as methanol extract of R. crategifolius roots are necessary for further studies as a potent inhibitor of the growth of cancer cells.

• Toxicological Research
• /
• 제23권2호
• /
• pp.135-142
• /
• 2007

Formononetin is an isoflavonoid phytoestrogen found in certain foodstuffs such as soy and red clover. In this study, we examined the action of formononetin with the carcinogen activation pathway mediated through the aryl hydrocarbon receptor (AhR) in MCF-7 breast carcinoma cells. Treating the cells with formononetin alone caused the accumulation of CYP1A1 mRNA as well as elevation in CYP1A1-specific 7-ethoxyresorufin O-deethylase (EROD) activity in a dose dependent manner. However, a concomitant treatment with 7,12-dimethylbenz[a]anthracene (DMBA) and formononetin markedly reduced both the DMBA-inducible EROD activity and CYP1A1 mRNA level. Under the same conditions, formononetin inhibited the DMBA-induced AhR transactivation, as shown by reporter gene analysis using a xenobiotic responsive element (XRE). Additionally, formononetin inhibited both DMBA-inducible nuclear localization of the aryl hydrocarbon receptor (AhR) and metabolic activation of DMBA, as measured by the formation of the DMBA-DNA adducts. Furthermore, formononetin competed with the prototypical AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), for binding to the AhR in an isolated rat cytosol. These results suggest that formononetin might be considered as a natural ligand to bind on AhR and consequently produces a potent protective effect against DMBA-induced genotoxicity. Therefore, that's the potential to act as a chemopreventive agent that is related to its effect on AhR pathway as antagonist/agonist.

• Archives of Pharmacal Research
• /
• 제29권7호
• /
• pp.570-576
• /
• 2006

Phytoestrogen biochanin A is an isoflavone derivative isolated from red clover Trifolium pratense with anticarcinogenic properties. This study examined the action of biochanin A with the carcinogen activation pathway that is mediated by the aryl hydrocarbon receptor (AhR) in MCF-7 breast carcinoma cells. Treating the cells with biochanin A alone caused the accumulation of CYP1A1 mRNA and an increase in CYP1A1-specific 7-ethoxyresorufin O-deethylase (EROD) activity in a dose dependent manner. A concomitant treatment with 7,12-dimethylbenz[a]anthracene (DMBA) and biochanin A markedly reduced the DMBA-inducible EROD activity and CYP1A1 mRNA level. In addition, the biochanin A treatment alone activated the DNA-binding capacity of the AhR for the dioxin-response element (DRE) of CYP1A1, as measured by the electrophoretic-mobility shift assay (EMSA). EMSA revealed that biochanin A reduced the level of the DMBA-inducible AhR-DRE binding complex. Furthermore, biochanin A competed with the prototypical AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), for binding to the AhR in an isolated rat cytosol. The biochanin A competitively inhibited the metabolic activation of DMBA, as measured by the formation of the DMBA-DNA adducts. These results suggest that biochanin A may thus be a natural ligand to bind on AhR. Therefore, biochanin A may be due to act an antagonist/agonist of the AhR pathway.

• 한국식품영양과학회지
• /
• 제38권2호
• /
• pp.142-145
• /
• 2009

산천어 70% 에탄올 추출물(MSE)이 암세포 성장억제와 Balb/c 마우스에서의 종양 성장 억제에 미치는 영향을 알아보았다. 인간 자궁암(HeLa), 간암(HepG2), 유방암(MCF-7), 위암(AGS), 폐암(A549) 세포 그리고 인간신장 정상세포 (293)에 MSE을 처리했을 때 세포생존율이 감소하였고 이들 감소율을 MTT assay로 알아보았다. MSE는 정상세포 293에서보다 인간 암세포주인 MCF-7, A549, HepG2, AGS 그리고 HeLa세포에서 현저하게 더 높은 세포독성이 나타났다. 시료 최고농도인 1 mg/mL를 인간 폐암세포(A549), 유방암세포(MCF-7), 간암세포(HepG2) 및 위암세포(AGS)에 처리한 결과 각각 9.2%, 12.7%, 14.6% 및 16.9%의 세포 생존율을 나타내었다. 더하여 복수암 세포(sarcoma-180)를 이용한 실험동물(Balb/c mice)에서의 고형암 성장 억제 효과를 알아보았으며, 각각 25 mg/kg body weight와 250 mg/kg body weight의 MSE를 투여하였을 때 종양 성장 억제율은 각각 44.7%와 55.7%였다. 따라서 우리는 MSE가 암 예방을 위해 인간에게 유익한 기능성 소재일 것이라는 것을 제안하였다.

• Nutrition Research and Practice
• /
• 제4권3호
• /
• pp.177-182
• /
• 2010

The Chaga mushroom (Inonotus obliquus) has been used in folk medicine to treat cancers. However, limited information exists on the underlying anticancer effects of the major component of I. obliquus in vivo. We hypothesize that the pure compounds ($3{\beta}$-hydroxy-lanosta-8,24-dien-21-al, inotodiol and lanosterol, respectively) separated from I. obliquus would inhibit tumor growth in Balbc/c mice bearing Sarcoma-180 cells (S-180) in vivo and growth of human carcinoma cells in vitro. To test this hypothesis, the growth inhibition of each subfraction isolated from I. obliquus on human carcinoma cell lines (lung carcinoma A-549 cells, stomach adenocarcinoma AGS cells, breast adenocarcinoma MCF-7 cells, and cervical adenocarcinoma HeLa cells) was tested in vitro. Then, after S-180 implantation, the mice were fed a normal chow supplemented with 0, 0.1 or 0.2 mg of subfraction 1, 2 or 3 per mouse per day. All of the subfractions isolated from I. obliquus showed significant cytotoxic activity against the selected cancer cell lines in vitro. Subfraction 1 was more active than subfraction 2 and subfraction 3 against the A549, AGS and MCF-7 cancer cell lines in vitro. In in vivo results, subfraction 1 isolated from I. obliquus at concentrations of 0.1 and 0.2 mg/mouse per day significantly decreased tumor volume by 23.96% and 33.71%, respectively, as compared with the control. Subfractions 2 and 3 also significantly inhibited tumor growth in mice bearing S-180 as compared with the control mouse tumor. Subfraction 1 isolated from I. obliquus showed greater inhibition of tumor growth than subfractions 2 and 3, which agrees well with the in vitro results. The results suggest that I. obliquus and its compounds in these subfractions isolated from I. obliquus could be used as natural anticancer ingredients in the food and/or pharmaceutical industry.

• 대한본초학회지
• /
• 제21권1호
• /
• pp.79-87
• /
• 2006

Objectives : Effects of Rhodiola rosea root on cancers on stomach, breast, lung, and liver were examined. Methods : Water extracts and methanol extracts of Rhodiola rosea root were treated on cancer cells, and its effects on cancers were examined. Results : 1. Water extracts and methanol extracts of Rhodiola rosea root was less harmful in its lowest density 0.25 mg/mL (9.l%와 10.5%), but became more harmful as its density increased. 2. As for human stomach adenocarcinoma cells AGS, breast adenocarcinoma cells MCF-7, and lung carcinoma cells A549, methanol extracts showed 70-77% inhibition of cancer cells in high density(1 mg/mL), and water extracts showed 60-70% inhibition rate and its selective death rate was less than 2.5. Conclusion : Rhodiola rosea root can be used to treat cancers and to increase immunity.

• IMMUNE NETWORK
• /
• 제2권1호
• /
• pp.19-24
• /
• 2002

Background: Salvia miltiorrhiza (SM), a traditional oriental medicine, has been reported to have anti-tumor properties, but its exact mechanism remains to be elucidated. In this study, we investigated several of the molecular events that occur in human breast carcinoma MCF-7 cells and human pulmonary adenocarcinoma A549 cells. Methods: For this purpose, we evaluated the growth-inhibitory effect of SM in association with the expressions of p53, p21, cyclin D1, and pRb, which are known to be involved in cell cycle arrest. The extent of thymidine incorporation was also examined to assess G1/S phase cell cycle arrest in both cells by $^3H$-thymidine incorporation. Results: Our results show that SM inhibits the growth and the proliferation of MCF-7 and A549 cells. Furthermore, we also observed increased expression of p21 via a p53-dependent pathway in both cell lines after treating with SM. In addition, treatment with SM for 24 hours caused the suppression of hyperphosphorylated retinoblastoma protein (pRb) expression and the dephosphorylation of pRb. Conclusion: These findings suggest that the growth inhibitory and the anti-proliferation effects of SM on MCF-7 cells and A549 cells are mediated via the decreased expression and dephosphorylation of pRB by p21 up-regulation in a p53-dependent manner. To the best of our knowledge, this study is the first to report upon the molecular mechanisms involved in SM-induced tumor cell growth inhibition.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권1호
• /
• pp.199-203
• /
• 2014

Background: Rosuvastatine, doxazosin, repaglinide and oxcarbazepin are therapeutic drugs available in the market for the treatment of different diseases. Potential to display antitumor activities has also been suggested. The aim of the current study was to evaluate their in vitro effects on some human transformed cell lines. Materials and Methods: Cytotoxicity of the four drugs was tested in MCF-7, HeLa and HepG2 cells by the neutral red assay method and also the effect of rosuvastatine and doxazosin against Ehrlich Ascities Carcinoma Cells (EACC) by trypan blue assay. Results: Rosuvastatine exerted the greatest cytotoxic effect against HepG2 cells with an $IC_{50}$ value of $58.7{\pm}69.3$; in contrast doxazosin showed least activity with $IC_{50}=104.4{\pm}115.7$. Repaglinide inhibited the growth of both HepG2 and HeLa cells with $IC_{50}$ values of $87.6{\pm}117.5$ and $89.3{\pm}119.5$, respectively. Oxcarbazepine showed a potent cytotoxicity against both HeLa ($IC_{50}=19.4{\pm}43.9$) and MCF7 cancer cells (($IC_{50}=22{\pm}35.7$).On the other hand the growth of EACC was completely inhibited by doxazosine (100% inhibition) while rosuvastatine had weak inhibitory activity (11.6%). Conclusions: The four tested drugs may have cytotoxic effects against hepatic, breast and cervical carcinoma cells; also doxazosine may inhibit the growth of endometrial cancer cells. Further investigations in animals are needed to confirm these results.

• 대한수의학회지
• /
• 제45권1호
• /
• pp.85-91
• /
• 2005

Much of the interest on the chemopreventive properties of herbs and plants has been raised, whereas little is regarding to anti-tumor effect of farming and aquatic products. In the present study, the anti-tumor effect of hot-water extract of a seaweed, BLC (Sargassum fulvellum) and BLC/HEN egg was investigated using MCF-7 cells in vitro and in vivo systems. We found that the BLC extract and BLC/HEN egg inhibited cell proliferation in a dose-dependent manner, which might be mediated through up-regulation of p53. Furthermore, this test compound can directly induce apoptosis in MCF-7 cells, which might be mediated through up-regulation of a pro-apoptotic Bax protein and down-regulation of a anti-apoptotic Bcl-2 protein, not by immune system. Nude mice bearing established breast tumors (with exogenous estradiol) were treated with BLC extract and BLC/HEN egg. Treatment BLC extract and BLC/HEN egg caused a 42% and 71% inhibition of tumor growth, respectively. Both agents caused a significant inhibition of volume and weight growth of estrogen independent human breast tumors established from MCF-7 cells. Our results suggested that BLC extract and BLC/HEN egg have the efficacious effect of human breast cancer not only in vitro but also in vivo.