[논문]마늘추출물에 의한 암세포의 이동 저하

김은경; 윤성지; 하정민; 진인혜; 김영환; 김선근; 박다정; 최영환; 윤식; 김치대; 배순식

doi:10.5352/jls.2011.21.6.767

마늘추출물에 의한 암세포의 이동 저하
Inhibition of Cancer Cell Migration by Compounds from Garlic Extracts 원문보기

생명과학회지 = Journal of life science, v.21 no.6 = no.134, 2011년, pp.767 - 774

초록
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세포의 이동은 많은 생리적 반응뿐만 아니라 암 세포 침윤과 전이에 중요한 역할을 수행한다. 본 연구에서는 마늘이 암세포의 이동에 미치는 영향을 확인하기 위해, 표준 마늘과 흑마늘을 준비하고 이들을 각각 물을 이용하여 추출하거나 건조하여 추출한 추출물 4 종류를 이용하여 항침윤성과 항전이성에 대해 조사하였다. 실험결과, 암세포의 이동은 건조 후 헥산으로 추출한 분획에 암세포의 이동 억제 활성이 관찰되었다. 이 분획을 박막 크로마토그래피를 이용하여 분리정제하였으며, 이를 inhibitor of cancer metastasis from garlic #27 (ICMG-27)이라 명명하였다. ICMG-27 (6 ${\mu}g/ml$)을 세포에 처리하였을 때, IGF-1에 의한 OVCAR-3와 NIH-3T3 세포의 이동을 억제함을 확인하였다. 그러나 ICMG-27은 mouse embryonic fibroblast (MEF) 세포에서 IGF-1에 의한 이동에는 영향을 주지 않았다. 이러한 ICMG-27은 OVCA-3, SKOV-3와 MDA-MB-231 세포와 같은 암세포에서 모두 IGF-1에 의한 이동을 억제함을 관찰하였다. 마지막으로 세포이동을 일으키는 인자에 따른 ICMG-27의 영향을 확인한 것으로, IGF-1, lysophosphatidic acid (LPA), sphingosine-1-phosphate (S1P), leukotriene B4 (LTB4) 그리고, angiotensinII (AngII)에 의한 OVCAR-3 세포의 이동을 모두 억제하였다. 이러한 결과를 바탕으로, ICMG-27은 암세포의 이동을 유도하는 많은 인자들에 의한 필수적인 단계를 차단함으로써, 암세포의 이동을 억제하는 것을 확인 할 수 있었으며, ICMG-27에 의한 암세포의 항 침윤 메커니즘의 규명은 암환자의 치료에 기초적인 발판을 제공할 것입니다.

Abstract ▼ AI-Helper

Cell migration plays a fundamental role in cancer cell invasion and metastasis as well as in many physiological responses. Here, we screened four different sources of garlic - water extract of normal and black garlic, as well as dried normal and black garlic - for the identification of anti-invasive and anti-metastatic activity on cancer cells. Inhibition of cancer cell migration was observed in the hexane extract of dried-garlic. Inhibitory activity was further purified to near homogeneity by thin layer chromatography and named $\b{i}$nhibitor of $\b{c}$ancer $\b{m}$etastasis from garlic #27 (ICMG-27). ICMG-27 completely blocked insulin-like growth factor-1 (IGF-1)-induced OVCAR-3 cell migration at 6 ${\mu}g/ml$. ICMG-27 completely blocked IGF-1-induced OVCAR-3 and NIH-3T3 cell migration whereas IGF-1-induced mouse embryonic fibroblast (MEF) cell migration was not affected byICMG-27. ICMG-27 inhibited all the tested IGF-1-induced cancer cell migration such as OVCAR-3, SKOV-3, and MDA-MB-231 cells. Finally, ICMG-27 could inhibit IGF-1-, lysophosphatidic acid (LPA)-, sphingosine-1-phosphate (S1P)-, leukotriene B4 (LTB4)-, and angiotensin II (AngII)-induced OVCAR-3 cell migration. These results indicate that ICMG-27 inhibits cancer cell migration by blocking essential steps in many agonists-induced cancer cell migrations. Unveiling an anti-invasive mechanism of ICMG-27 on cancer cells will provide a basis for cancer therapy.

주제어

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가설 설정

Despite the abundant in vitro evidence for anti-cancer effect of garlic extracts, anti-metastatic effect of garlic extract or its compounds is not well studied. In this study, we provide novel anti-metastatic activity from hexane fractions of dried garlic. Nearly pure compound of this agent inhibited variety of cancer cell migration.

제안 방법

(A) OVCAR-3, SKOV-3, and MDAMB-231 cells were stimulated with IGF-1 (50 ng/ml) in the presence or absence of ICMG-27 (10 μg/ml) and measured migration (B) OVCAR-3 cells were stimulated with IGF-1 (50 ng/ml), LPA (10 μM), S1P (100 nM), LTB4 (100 nM), and AngII (10 μM) in the presence or absence of ICMG-27 (10 μg/ml) followed by measuring migration as described in “Materials and Methods” Data are the mean±S.D. of three independent experiments (n=3 for each experiment).
Among the thin layer chromatographic fractions, #27 fraction (inhibitor of cancer metastasis from garlic #27, named ICMG-27) was revealed to single compound as judged by the analysis of NMR spectra (Fig. 2C), and strongly inhibited IGF-1-induced cancer cell migration (Fig. 2B).
Cell lysates were subjected to 8-15% gradient polyacrylamide gel electrophoresis and transferred onto a nitrocellulose membrane. Membranes were incubated with the indicated primary antibodies and IRDye-conjugated secondary antibodies, and protein bands were visualized using an Infrared image analyzer (Li-COR Bioscience).

대상 데이터

Dulbecco's modified Eagle's medium (DMEM), fetal bovine serum (FBS), trypsin-EDTA, and antibiotics were purchased from Hyclone Laboratories Inc (Logan, UT, USA). Anti-phospho-Akt (Ser473) and anti-phospho-Akt (Thr308) were purchased from Cell Signaling Technology (Boston, MA, USA). IRDye700- and IRDye800-conjugated rabbit/mouse secondary antibodies were obtained from Li-COR Bioscience (Lincoln, NE, USA).
IRDye700- and IRDye800-conjugated rabbit/mouse secondary antibodies were obtained from Li-COR Bioscience (Lincoln, NE, USA). IGF-1, lysophosphatidic acid (LPA), and angiotensin II (AngII) were purchased from Sigma-Aldrich (St. Louis, MO, USA). Leukotriene B4 (LTB4) was obtained from Cayman (Ann Arbor, MI, USA).

데이터처리

When comparing two groups, an unpaired Student’s t-test was used to assess differences.

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저자의 다른 논문 :

표제어: PCR

동의어: Packet Collision Rate

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용어 설명: PCR은 세균 특이성이 있는 primer를 이용하여 적은 수의 세균이 있을지라도 쉽게 검출할 수 있는 유용한 방법이며, 이를 이용하여 구강 내 치면세균막이나 타액에서 직접 세균을 검출할 수 있게 되었다[8].

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