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마늘추출물에 의한 암세포의 이동 저하

Inhibition of Cancer Cell Migration by Compounds from Garlic Extracts

  • 김은경 (허혈조직재생연구센터, 부산대학교 의학전문대학원 약리학교실) ;
  • 윤성지 (허혈조직재생연구센터, 부산대학교 의학전문대학원 약리학교실) ;
  • 하정민 (허혈조직재생연구센터, 부산대학교 의학전문대학원 약리학교실) ;
  • 진인혜 (허혈조직재생연구센터, 부산대학교 의학전문대학원 약리학교실) ;
  • 김영환 (허혈조직재생연구센터, 부산대학교 의학전문대학원 약리학교실) ;
  • 김선근 (부산대학교 생명자원과학대학) ;
  • 박다정 (부산대학교 생명자원과학대학) ;
  • 최영환 (부산대학교 생명자원과학대학) ;
  • 윤식 (부산대학교 의학전문대학원 해부학교실) ;
  • 김치대 (허혈조직재생연구센터, 부산대학교 의학전문대학원 약리학교실) ;
  • 배순식 (허혈조직재생연구센터, 부산대학교 의학전문대학원 약리학교실)
  • Kim, Eun-Kyoung (MRC for Ischemic Tissue Regeneration, Medical Research Institute, Department of Pharmacology, Pusan National University School of Medicine) ;
  • Yun, Sung-Ji (MRC for Ischemic Tissue Regeneration, Medical Research Institute, Department of Pharmacology, Pusan National University School of Medicine) ;
  • Ha, Jung-Min (MRC for Ischemic Tissue Regeneration, Medical Research Institute, Department of Pharmacology, Pusan National University School of Medicine) ;
  • Jin, In-Hye (MRC for Ischemic Tissue Regeneration, Medical Research Institute, Department of Pharmacology, Pusan National University School of Medicine) ;
  • Kim, Young-Whan (MRC for Ischemic Tissue Regeneration, Medical Research Institute, Department of Pharmacology, Pusan National University School of Medicine) ;
  • Kim, Sun-Gun (Department of Natural Resources and Life Sciences, Pusan National University) ;
  • Park, Da-Jung (Department of Natural Resources and Life Sciences, Pusan National University) ;
  • Choi, Young-Whan (Department of Natural Resources and Life Sciences, Pusan National University) ;
  • Yun, Sik (Department of Anatomy, Pusan National School of Medicine) ;
  • Kim, Chi-Dae (MRC for Ischemic Tissue Regeneration, Medical Research Institute, Department of Pharmacology, Pusan National University School of Medicine) ;
  • Bae, Sun-Sik (MRC for Ischemic Tissue Regeneration, Medical Research Institute, Department of Pharmacology, Pusan National University School of Medicine)
  • 투고 : 2011.03.22
  • 심사 : 2011.04.13
  • 발행 : 2011.06.30

초록

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.

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.

키워드

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  1. Correlations between Soil Environment and Bioactive Constituents of Namdo Garlic Harvested in the Non-volcanic Ash Soil Distributed Western Jeju vol.23, pp.2, 2015, https://doi.org/10.7783/KJMCS.2015.23.2.125
  2. Anti-metastatic Effect of Garlic Hexane Extract on Lung Metastasis Induced by Melanoma B16F10 Cells in Mice vol.26, pp.2, 2016, https://doi.org/10.5352/JLS.2016.26.2.259