천마 추출물을 처리한 간암 세포에서 Bcl-2, Bax 및 AMPKα 발현과 세포 자멸사에 미치는 영향 분석
Effects of Gastrodia elata Blume on Apoptotic Cell Death of Liver Cancer Cells by Expression of Bcl-2, Bax, and AMPKα
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background: This study was carried out to investigate the anticancer effects of Gastrodia elata Blume extract (GEE) in human hepatoma-derived Hep3B cells by apoptotic cell death. Methods and Results: To evaluate the anticancer effect, a Hep3B cell viability assay and a realtime quantitative reverse transcription polymerase chain reaction (qRT-PCR) on GEE were performed, which was obtained extracted by ultrasound-assisted extraction and then used to treat the Hep3B cells. Cell viability was inhibited to 48.2% (4.0 ㎎/㎖). To identify anticancer mechanisms using qRT-PCR, mRNA expressions of B-cell lymphoma-2, its associated Bax protein, and 5’- AMP-activated protein kinase were examined with a comparative △CT method. A qualitative analysis of the bioactive compounds in GEE was coducted using liquid chromatography tandem mass spectrometry, gastrodin and phloretin were identified as the two major compounds. Conclusions: These findings demonstrate that GEE can decrease liver cancer cell viability and control apoptosis gene expression to have anticancer effects, GEE could be employed as a natural anticancer agent with less side effects than those of traditional anticancer medications.
Abstract
Background: This study was carried out to investigate the anticancer effects of Gastrodia elata Blume extract (GEE) in human hepatoma-derived Hep3B cells by apoptotic cell death. Methods and Results: To evaluate the anticancer effect, a Hep3B cell viability assay and a realtime quantitative reverse transcription polymerase chain reaction (qRT-PCR) on GEE were performed, which was obtained extracted by ultrasound-assisted extraction and then used to treat the Hep3B cells. Cell viability was inhibited to 48.2% (4.0 ㎎/㎖). To identify anticancer mechanisms using qRT-PCR, mRNA expressions of B-cell lymphoma-2, its associated Bax protein, and 5’- AMP-activated protein kinase were examined with a comparative △CT method. A qualitative analysis of the bioactive compounds in GEE was coducted using liquid chromatography tandem mass spectrometry, gastrodin and phloretin were identified as the two major compounds. Conclusions: These findings demonstrate that GEE can decrease liver cancer cell viability and control apoptosis gene expression to have anticancer effects, GEE could be employed as a natural anticancer agent with less side effects than those of traditional anticancer medications.
참고문헌 (38)
- Alnemri ES, "Mammalian cell death proteases : A family of highly conserved aspartate specific cysteine proteases", Journal of Cellular Biochemistry, 64, pp.33~42 (1997)
- Borger DR, "AMP-activated protein kinase is essential for survival in chronic hypoxia", Biochemical and Biophysical ResearchCommunications, 370, pp.230~234 (2008)
- 최영주, "모링가 잎 추출물의 항당뇨, 알코올 대사 및 간 보호 활성", 한국식품영양과학회지, 45(6), pp.819~827 (2016), 한국식품영양과학회
- Duan H, "Phloretin induces apoptosis of human esophageal cancer via a mitochondria-dependent pathway", Oncology Letters, 14, pp.6763~6768 (2017)
- Ernst E, "The prevalence of complementary", alternative medicine in cancer : A systematic review, 1998, pp.83, 777~782
- Festuccia C, "Epidermal growth factor modulates prostate cancer cell invasiveness regulating urokinase-type plasminogen activator activity", Thrombosis and Haemostasis, 93, pp.964~975 (2005)
- Fogarty S, "Development of protein kinase activators : AMPK as a target in metabolic disorders and cancer", Biochimica et Biophysica Acta(BBA)-Proteins and Proteomics, 1804, pp.581~591 (2010)
- Han X., "Protective effect of gastrodin on myocardial ischemia-reperfusion injury and the expression of Bax and Bcl-2", Experimental and Therapeutic Medicine, 17, pp.4389~4394 (2019)
- 허진철, "천마추출물의 항산화 및 항암 활성", Food Science and Preservation, 13(1), pp.83~87 (2006), 한국식품저장유통학회
- Hockenbery D, "Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death", Nature, 348, pp.334~336 (1990)
- 홍주희, "Bcl-2의 저해제 처리에 따른 돼지 수정란의 배발달 능력, 세포 사멸 및 소포체 스트레스 양상", Reproductive & Developmental biology, 36(3), pp.167~172 (2012), 사단법인 한국동물생명공학회
- Huang WC, "Phloretin attenuates allergic airway inflammation and oxidative stress in asthmatic mice", Frontiers in Immunology, 8, pp.134~ (2017)[DOI]
- Jin Z, "Overview of cell death signaling pathways", Cancer Biology and Therapy, 4, pp.147~171 (2005)
- Kang HG, "Expressions of apoptotic genes(survivin, Bcl-2, Bax)and clinical relevance in osteosarcoma", Journal of the Korean Bone and Joint Tumor Society, 11, pp.118~125 (2005)
- 김은지, "Hep3B 간암세포에서 개똥쑥추출물로부터 Akt-mTOR-GSK3β 신호경로에 의한 apoptosis 효과", 생명과학회지, 26(7), pp.764~771 (2016), 한국생명과학회
- 김은숙, "그레이브스병에서 조절 T 세포에 의한 병원성 자가항원반응성 CD4+ T 세포의 억제효과", Endocrinology and Metabolism, 22(5), pp.332~338 (2007), 대한내분비학회
- 김준세, "인간 섬유육종세포에서 비쑥 추출물과 유기용매 분획물의 암전이 억제 효과", 생명과학회지, 31(12), pp.1100~1109 (2021), 한국생명과학회[DOI]
- 김경동, "약용식물의 부위별 및 추출용매에 따른 효능 연구", 대한화장품학회지, 33(2), pp.127~135 (2007), 사단법인 대한화장품학회
- 김민영, "Relationship between Reactive Oxygen Species and Adenosine Monophosphate-activated Protein Kinase Signaling in Apoptosis Induction of Human Breast Adenocarcinoma MDA-MB-231 Cells by Ethanol Extract of Citrus unshiu Peel", 생명과학회지, 29(4), pp.410~420 (2019), 한국생명과학회[DOI]
- Koh HJ, "AMPK links energy status to cell structure and mitosis", Biochemical and Biophysical Research Communications, 362, pp.789~792 (2007)
- Korsmeyer SJ, "Bcl-2", Bax : A rheostat that regulates an anti-oxidant pathway and cell death, 1993, pp.4, 327~332
- 이홍구, "천마꽃 추출물의 항산화, 항염, 보습 활성에 대한 연구", 대한화장품학회지, 47(3), pp.219~226 (2021), 사단법인 대한화장품학회
- 이명선, "천마(Gastrodia elate)로부터 분리한 VHR DS-PTPase 저해 물질", 한국식품과학회지, 34(3), pp.505~509 (2002), 한국식품과학회
- Shin Hwa Lee, "염증-치주 질환과 암에 관한 최근 연구 동향", 생명과학회지, 24(4), pp.602~608 (2013), 한국생명과학회[DOI]
- Liu XC, "Gastrodin attenuates neuronal apoptosis and neurological deficits after experimental intracerebral hemorrhage", Journal of Stroke and Cerebrovascular Diseases, 29, pp.104483~ (2020)[DOI]
- Livak KJ, "Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method", Methods, 25, pp.402~408 (2001)
- Lv Y, "Effects of gastrodin on BV2 cells under oxygen-glucose deprivation and its mechanism", Gene, 766, pp.145152~ (2021)[DOI]
- Montalto G, "Epidemiology, risk factors, and natural history of hepatocellular carcinoma", Annals of the New York Academy of Sciences, 963, pp.13~20 (2002)
- Okada E, "Survivin expression in tumor cell nuclei is predictive of a favorable prognosis in gastric cancer patients", Cancer Letters, 163, pp.109~116 (2001)
- Park W, "Local radiotherapy for patients with unresectable hepatocellular carcinoma", International Journal of Radiation Oncology*Biology*Physics, 61, pp.1143~1150 (2005)
- Shu G, "Gastrodin stimulates anticancer immune response and represses transplanted H22 hepatic ascitic tumor cell growth : Involvement of NF-κB signaling activation in CD4+ T cells", Toxicology and Applied Pharmacology, 269, pp.270~279 (2013)
- 송영화, "대장암에서 세포자멸사 유발성 bcl-2 Family 유전자의 돌연변이 연구", Journal of Pathology and Translational Medicine, 39(3), pp.168~171 (2005), 대한병리학회
- "Statistics on the cause of death in 2020" (2021)[URL]
- Stuver SO., "Towards global control of liver cancer?", Seminars in Cancer Biology, 8, pp.299~306 (1998)
- Wang ZH, "Herbal decoction of Gastrodia, Uncaria, and Curcuma confers neuroprotection against cerebral ischemia in vitro and in vivo", Journal of Integrative Neuroscience, 19, pp.513~519 (2020)
- 윤유석, "천마가 중대뇌동맥 폐쇄 흰쥐의 신경세포 자연사에 미치는 영향", 한방재활의학과학회지, 19(3), pp.1~13 (2009), 한방재활의학과학회
- Zhao ZQ, "Adenosine attenuates reperfusion-induced apoptotic cell death by modulating expression of Bcl-2 and Bax proteins", Journal of Molecular and Cellular Cardiology, 33, pp.57~68 (2001)
- Zhishen J, "The determination of flavonoid contents in mulberry and their scavenging effects on superoxide radicals", Food Chemistry, 64, pp.555~559 (1999)