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생명과학회지 = Journal of life science v.18 no.1 = no.93, 2008년, pp.120 - 128   피인용횟수: 6

지금초 추출물에 의한 TRAIL 저항성 인체위암세포의 세포사멸 유도
Euphorbiae Immifusae Sensitizes Apoptosis of TRAIL-resistant Human Gastric Adenocarcinoma AGS Cells

이재준   (동의대학교 한의과대학 내과학교실UU0000509  ); 신동역   (동의대학교 생화학교실 및 대학원 바이오물질제어학과UU0000509  ); 박상은   (동의대학교 한의과대학 내과학교실UU0000509  ); 김원일   (동의대학교 한의과대학 내과학교실UU0000509  ); 박동일   (동의대학교 한의과대학 내과학교실UU0000509  ); 최영현   (동의대학교 생화학교실 및 대학원 바이오물질제어학과UU0000509  ); 홍상훈   (동의대학교 한의과대학 내과학교실UU0000509  );
  • 초록

    본 연구에서는 지금초 열수 추출물(WEEH)의 처리에 의한 TRAIL 저항성 인체 위암세포의 증식 억제와 연관된 apoptosis유발에 관한 기전 해석을 시도하였다. 이를 위하여 AGS 세포주가 사용되었으며 다음과 같은 결과를 얻었다. 본 연구에서 조사된 범위 내에서의 TRAIL (200 ng/ml) 및 WEEH (0.04 mg/ml)의 단독 처리에 의한 AGS 세포에 유의적인 세포 독성을 나타내지 않았다. 그러나 TRAIL 및 WEEH의 혼합 처리는 WEEH의 처리 농도의존적으로 AGS 세포의 증식을 억제하였으며, 이는 apoptosis 유발에 의한 것임을 MTT assay, 핵의 염색질 응축 및 세포주기 sub-G1기에 속하는 세포빈도의 증가 등으로 확인하였다. TRAIL 및 WEEH 혼합 처리에 의한 apoptosis 유발 기전의 해석을 위하여 다양한 생화학적 분석법에 의하여 조사된 결과에 의하면, TRAIL 및 WEEH 혼합처리에 의한 caspase-8의 활성화에 의한 BID의 truncation화 및 이와 연관된 미토콘드리아 기능의 손상에 따른 caspase-9의 활성화와 연관성이 있었다. 이러한 미토콘드리아 기능 손상 및 caspase-9의 활성화는 Bcl-2, Bcl-xL, XIAP 및 cIAP-2등과 같은 anti-apoptotic 인자들의 발현 저하와 연관성이 있는 것이며, 이로 인한 caspase-3의 활성화에 의한 PARP 단백질의 단편화 유도로 apoptosis가 일어난 것으로 예측되어 진다. 비록 부가적인 연구들이 요구되어지지만, 본 연구의 결과는 TRAIL저항성 암세포의 항암전략에 지금초 추출물의 적용 가능성을 보여주는 것으로서 지금초의 항암작용의 규명에 중요한 자료를 제공하여 줄 것으로 생각된다.

    The death ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/ Apo1L is a cytokine that activates apoptosis through cell surface death receptors. TRAIL has sparked growing interest in oncology due to its reported ability to selectively trigger cancer cell death. Euphorbiae humifusae Wind has been used in traditional Oriental medicine as a folk remedy used for the treatment of cancer. However, the mechanism responsible for the anticancer effects of E. humifusae not clearly understood. Here, we show that treatment with subtoxic doses of water extract of E. humifusae (WEEH) in combination with TRAIL induces apoptosis in TRAIL-resistant human gastric carcinoma AGS cells. Combined treatment with WEEH and TRAIL induced chromatin condensation and sub-G1 phase DNA content. These indicators of apoptosis were correlated with the induction of caspase activity that resulted in the cleavage of poly (ADP-ribose) polymerase. Combined treatment also triggered the loss of mitochondrial membrane potential. Furthermore, co-treatment with WEEH and TRAIL down-regulated the protein levels of the anti-apoptotic proteins such as Bcl-2, Bcl-xL, XIAP and cIAP-1. Although more study will be needed to examine the detailed mechanisms, this combined treatment may offer an attractive strategy for safely treating gastric adenocarcinomas and the results provide important new insights into the possible molecular mechanisms of the anticancer activity of E. humifusae.

  • 주제어

    Euphorbiae humifusae .   TNF-related apoptosis-inducing ligand(TRAIL) .   apoptosis .   mitochondrial membrane potential .   caspase.  

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    1. Hwang, Sung-Yeoun ; Ahn, Seong-Hun ; Keum, Kyung-Sao 2009. "Proposal on Spplementation to Oriental Medical Policy for the Revitalization of Oriental Medical Therapy for Stomach Cancer" 동의생리병리학회지 = Journal of physiology & pathology in Korean Medicine, 23(3): 528~533     
    2. Jeong, Myoung-Hoon ; Kim, Seung-Seop ; Ha, Ji-Hye ; Jin, Ling ; Lee, Hak-Ju ; Kang, Ha-Young ; Park, Sung-Jin ; Lee, Hyeon-Yong 2009. "Enhancement of Anticancer Activity of Acer mono by High Pressure Extraction Process" 한국식품영양과학회지 = Journal of the Korean Society of Food Science and Nutrition, 38(9): 1243~1252     
    3. Ha, Ji-Hye ; Jeong, Hyang-Suk ; Jeong, Myoung-Hoon ; Kim, Seung-Seop ; Jin, Ling ; Nam, Jong-Hyun ; Hwang, Baik ; Ma, Choong-Je ; Lee, Hyeon-Yong 2009. "Comparison of Anticancer Activities of Ultrasonification Extracts of Callus and Roots from Rhodiola sachalinensis A. Bor" 한국식품과학회지 = Korean journal of food science and technology, 41(5): 552~559     
    4. Ha, Ji-Hye ; Jeong, Myeong-Hoon ; Seo, Yong-Chang ; Choi, Woon-Yong ; Jeong, Heon-Sang ; Jung, Jae-Hyun ; Yu, Kwang-Wan ; Lee, Hyeon-Yong 2010. "Enhancement of Anticancer Activities of Low Quality Ginseng by Phelinus linteus Fermentation" 韓國藥用作物學會誌 = Korean journal of medicinal crop science, 18(3): 135~142     
    5. Park, Myoung-Su ; Jeong, Bo-Reum ; Bahk, Gyung-Jin 2015. "Antioxidant Activity and Cytotoxicity of Ethanol Extracts from Different Parts of Taraxacum coreanum Nakai cultivated in South Korea" 한국식품영양학회지 = The Korean journal of food and nutrition, 28(4): 594~601     
    6. Park, Myoung-Su ; So, Ji-Sun ; Bahk, Gyung-Jin 2015. "Antioxidative and Anticancer Activities of Water Extracts from Different Parts of Taraxacum coreanum Nakai Cultivated in Korea" 한국식품영양과학회지 = Journal of the Korean Society of Food Science and Nutrition, 44(8): 1234~1240     

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