Journal of the Korean Society of Food Science and Nutrition (한국식품영양과학회지)

The Korean Society of Food Science and Nutrition (한국식품영양과학회)
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Cytotoxic Effects of Tenebrio molitor Larval Extracts against Hepatocellular Carcinoma

갈색거저리 유충 추출물의 간암세포에 대한 세포독성 효능

  • Lee, Ji-Eun (Department of Biological Sciences, Ulsan National Institute of Science and Technology) ;
  • Lee, An-Jung (Department of Biological Sciences, Ulsan National Institute of Science and Technology) ;
  • Jo, Da-Eun (Department of Biological Sciences, Ulsan National Institute of Science and Technology) ;
  • Cho, Ju Hyeong (Department of Biological Sciences, Ulsan National Institute of Science and Technology) ;
  • Youn, Kumju (Department of Food Science and Nutrition, Dong-A University) ;
  • Yun, Eun-Young (Department of Agricultural Biology, National Academy of Agricultural Science, RDA) ;
  • Hwang, Jae-Sam (Department of Agricultural Biology, National Academy of Agricultural Science, RDA) ;
  • Jun, Mira (Department of Food Science and Nutrition, Dong-A University) ;
  • Kang, Byoung Heon (Department of Biological Sciences, Ulsan National Institute of Science and Technology)
  • 이지은 (울산과학기술대학교 생명과학과) ;
  • 이안중 (울산과학기술대학교 생명과학과) ;
  • 조다은 (울산과학기술대학교 생명과학과) ;
  • 조주형 (울산과학기술대학교 생명과학과) ;
  • 윤금주 (동아대학교 식품영양학과) ;
  • 윤은영 (농촌진흥청 곤충산업과) ;
  • 황재삼 (농촌진흥청 곤충산업과) ;
  • 전미라 (동아대학교 식품영양학과) ;
  • 강병헌 (울산과학기술대학교 생명과학과)
  • Received : 2014.10.02
  • Accepted : 2015.01.05
  • Published : 2015.02.28
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Abstract

Various natural products or their derivatives, mostly originating from plants, fungi, and bacteria, have been exploited as therapeutic drugs to treat various human diseases. In addition to previously explored organisms, research on natural compounds has now expanded into unexamined living organisms in order to identify novel bioactive substances. Here, we determined whether or not the larval form of the mealworm beetle Tenebrio molitor, a species of darkling beetle, contains cytotoxic substances that exclusively affect cancer cell viability. Ethanol extract and its solvent partitioned fractions, hexane and ethyl acetate fractions, showed anticancer effects against various human cancer cells derived from the prostate (PC3 and 22Rv1), cervix (HeLa), liver (PLC/PRF5, HepG2, Hep3B, and SK-HEP-1), colon (HCT116), lung (NCI-H460), breast (MDA-MB231), and ovary (SKOV3). Cell death induced by the fractions was a mix of apoptosis, necrosis, and autophagy. The hexane fraction was administered intraperitoneally to nude mice bearing a hepatocellular carcinoma SK-HEP-1 and showed inhibition of tumor growth in vivo. Therefore, we concluded that worm extracts contain cytotoxic substances, which can be enriched by proper fractionation protocols, and further separation and purification could lead to the identification of novel molecules to treat human cancers.

본 연구에서 우리는 갈색거저리 유충 추출물의 암세포 선택적인 세포독성 활성을 암세포주를 대상으로 하는 in vitro 및 in vivo 실험으로 증명하였다. 먼저 갈색거저리 유충의 에탄올 추출물은 정상세포라 할 수 있는 primary hepatocyte에 대한 독성은 미미하였으나 암세포주들에 대한 세포독성과 함께 다른 정상세포인 primary cardiomyocyte에 대한 독성도 가지고 있었다. 에탄올 추출물을 hexane, butanol, ethyl acetate, 물을 이용하여 liquid-liquid partition으로 추가로 분획, 구성물질들을 분리하였고 이들 분획물 중에서 hexane 분획물은 다양한 암세포들(PC3, 22Rv1, HeLa, PLC/PRF5, HepG2, Hep3B, SK-HEP-1, HCT116, NCI-H460, MDA-MB231, SKOV3)에 대한 독성을 유지하면서 cardiomyocyte에 대한 독성이 상당히 줄어들었다. 0.4 mg/mL 에탄올 추출물이 cardiomyocyte를 대부분 죽이는 독성을 보였으나 동일조건에서 hexane 분획물은 약 20% 정도의 세포독성만을 보여주어 독성이 상당히 감소된 것을 확인하였다. 이렇게 비특이적인 세포독성이 물질분리 및 분획을 함으로써 줄어들 수 있다는 것을 확인하였다. 두 번째로 hexane과 ethyl acetate 분획물들이 아포토시스, 세포괴사, 오토파지와 같은 대표적인 세포죽음 기전들을 활성화시킬 수 있는 것으로 확인하였다. 더불어 hexane 분획물의 세포죽음 유도활성은 현재 임상에서 널리 처방되고 있는 항암물질들과 함께 간암세포주에 처리되었을 때 항암활성을 증대시킬 수 있는 것으로 확인하였다. 이와 같은 실험 결과를 바탕으로 갈색거저리 유충 추출물들이 단독으로 혹은 다른 세포독성 약물들과 함께 항암활성을 가질 수 있음을 확인하였다. 마지막으로 hexane 분획물의 항암활성을 in vivo xenograft 실험쥐 모델에서 확인하였는데, 간암세포주인 SK-HEP-1을 이식한 실험쥐에서 hexane 분획물을 15일간 복강주사 하였을 때 종양의 성장을 뚜렷하게 억제하는 것을 확인하였고, 앞선 정상세포에 대한 제한적인 영향과 일치하게 몸무게의 감소 등 부작용이라 할 수 있는 증상은 확인되지 않았다. 이상의 결과들을 종합하면 갈색거저리 유충 추출물의 항암활성을 in vitro와 in vivo에서 확인할 수 있었으며, 새로운 항암활성을 가지는 물질 발굴을 위해 추가적인 분획과 물질 분석이 필요하다고 사료된다.

Keywords

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