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      • The ginsenoside metabolite compound K inhibits hormone-independent breast cancer through downregulation of cyclin D1

        Lee, Seung Joon,Lee, Ji Su,Lee, Eunjung,Lim, Tae-Gyu,Byun, Sanguine Elsevier 2018 Journal of Functional Foods Vol.46 No.-

        <P><B>Abstract</B></P> <P>Various types of ginsenosides are present in ginseng and have been recognized for their health-promoting effects.Compound K (CK) is a metabolite ofginsenoside Rb1 and reportedly exerts chemotherapeutic effects against several types of cancers. However, the anti-cancer effect and the molecular mechanism of CK against hormone-independent breast cancer is unknown. Through a direct comparison, it was discovered that CK elicits the strongest anti-cancer effect against breast cancer cells when compared to other ginsenosides. CK treatment suppresses the growth of hormone-independent human breast cancer cells and induces G1 phase cell cycle arrest. CK also markedly suppresses tumor growth in a mouse xenograft model, concomitant with the suppression of cyclin D1 via protein degradation. These findings suggest that CK can be used to target hormone-independent breast cancers by inducing degradation of cyclin D1.</P> <P><B>Highlights</B></P> <P> <UL> <LI> CK is the most potent ginsenoside against breast cancer. </LI> <LI> CK inhibits breast cancer tumor growth <I>in vivo.</I> </LI> <LI> CK induces G1 cell cycle arrest in hormone-independent breast cancer cells. </LI> <LI> CK suppresses cyclin D1 expression through proteasomal degradation. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

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        대두와 현미 추출몰이 호르몬 의존형 및 비의큰형 유방암세포의 성장에 미치는 영향

        성미경,박미영 한국식품영양과학회 2002 한국식품영양과학회지 Vol.31 No.3

        대두(백태,흑태)와 현미의 메탄올과 아세톤 추출물이 호르몬 의존형 유방암세포(MCF-7)와 호르몬 비의존형세포(MDA-MB-231)의 세포독성과 apoptosis에 미치는 영향을 살펴보았다 각 추출물별 25, 50, 100 ug/well의 농도로 24, 48, 72시간 배양 시 배양시간과 사용된 시료 모두 농도 의존적으로 유방암 세포생존율을 억제하는 것으로 나타났다. 특히 호르몬 의존형 세포인 MCF-7 에서는 현미의 아세톤 추출물이 낮은 농도에서 짧은 배양시간에도 그 효과가 나타났고 호르몬 비의존형 세포주 MDA-MB-231에서는 현미의 아세톤 및 메탄올 추출물의 효과가 다른 시료들에 비해 높게 나타났다. Apoptosis에 미치는 영향에서는 호르몬 비의존형 세포(MDA-MB-231)에서 메탄올추출물 처리군이 대조군에 비해 apoptosis된 세포가 유의적으로 증가한 것을 관찰할 수 있었다. 그러나 세포생존율 결과와는 다르게 호르몬의존형 세포와 호르몬비의존형 세포 모두에서 아세톤 처리군은 대조군에 비해 apptosis에 유의차를 나타내지 않았다. 이상의 결과에 의하면 이들 화합물이 소유한 암세포 성장억제 기전은 추출물내 함유된 화합물의 종류와 세포성장의 호르몬 의존도에 따라 다양한 것으로 사료된다. A number of experimental and epidemiological studies have implicated that antiestrogenic effects of estrogen-like compounds in legumes and plant seeds are responsible for lowering breast cancer risk in human. However, few studies have been conducted to illustrate the possible chemopreventive effects of Korean traditional food materials. This study was performed to determine the cytotoxic and apoptotic effects of yellow soybeans, black soybeans and brown rice extracts on hormone-dependent and hormone-independent human breast cancer cells. Methanol-or acetone-soluble fractions of soybeans or brown rice were incubated with hormone-dependent cells (MCF-7) or hormone-independent cells (MDA-MB-231). Cell cytotoxicity was measured by MTT assay at 24, 48 and 72 hrs of incubation. Apoptotic effects of these extracts toward breast cancer cells were also determined at 48 hrs of incubation by measuring DNA fragmentation. Results indicated that the acetone-soluble fraction of brown rice exerted strongest cytotoxic effect on MCF-7 ceIls, although other fractions also reduced the number of viable MCF-7 cells after 48 hrs of incubation. Both acetone and methanol soluble fractions of all samples exerted a significant cytotoxicity towards MDA-MB-231 cells after 24 hrs of incubation, and acetone and methanol soluble fractions of brown rice were especially effective in these cells. At 48 hrs of incubation, methanol fractions of all three samples induced apopotosis of MDA-MB-231 cells. These results indicate methaol or acetone soluble fractions of yellow soybeans, black soybeans and brown rice induce cytotoxicity in both hormone-dependent and hormone-independent breast cancer cells. Therefore, possible mechanisms of cell cytotoxicity do not necessarily include antiestrogenic effects of soybean or brown rice extract. A possible anticarcinogenic effect of brown rice methanol-soluble fraction may mediated through their apoptotic effect. Further studies are requried to elucidate responsible compounds and mechanisms involved in observed anticarcinogenesis.

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