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후코이단/이고들빼기 혼합물에 의한 HepG2 간암세포의 apoptosis 유도

Induction of apoptosis using the mixture of fucoidan and Crepidiastrum denticulatum extract in HepG2 liver cancer cells

김한중|박형범|김기만|최다빈|박세은|오교녀
한국식품저장유통학회 (The Korean Society of Food Preservation)|2024.04|Food Science and Preservation|제31권 제2호|pp. 276-286|DOI 10.11002/fsp.2024.31.2.276

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apoptosisfucoidanCrepidiastrum denticulatum extractHepG2 human liver cancer cell
주제분류식품과학

초록

본 연구에서는 후코이단/이고들빼기 혼합물이 HepG2 세포의 apoptosis에 미치는 영향을 확인하고 어떠한 경로를 통해 나타나는지를 조사하였다. 후코이단/이고들빼기 혼합물이 HepG2 세포의 증식을 억제하고 세포 독성을 나타냈다. 이러한 HepG2 세포의 증식 억제 및 세포 독성이 apoptosis에 의한 효과인지를 확인한 결과, DNA fragmentation과 mitochondria membrane potential의 저해를 일으키는 것을 확인하였다. 이러한 결과를 바탕으로 HepG2 세포에서 후코이단/이고들빼기 혼합물이 apoptosis를 유도하는 기전에 관여하는 단백질의 발현 양상을 확인한 결과, intrinsic apoptosis 경로인 p53을 증가시키고, Bcl-2 family인 Bcl-2의 억제 및 BAX의 증가를 통해서 cytochrome c를 증가시켜 caspase-9 활성화하였고, caspase-3를 활성화시켜 결과적으로 apoptosis를 유도하였다. 또한, 전반적으로 후코이단/이고들빼기 혼합물의 apoptosis 유도 효과는 후코이단만 처리한 것보다 더 높은 효과를 나타냈으며, 이는 이고들빼기 추출물과의 혼합물 제조를 통해서 후코이단의 apoptosis 유도 효과가 증대되는 것으로 판단된다. 이러한 결과는 후코이단/이고들빼기 혼합물이 HepG2 세포에서 apoptosis 관련 유전자의 발현 조절에 의해 항암 효과를 나타내며, 이는 후코이단/이고들빼기 혼합물의 항암 작용의 기전을 해석하였을 뿐만 아니라, 이러한 기전 연구를 바탕으로 실질적인 간암 치료제로서의 사용 가능성을 확인하기 위해서는 유용 물질 분석 및 in vivo에서 추가 실험 등이 다양하게 수행되어야 할 것으로 판단된다.

Abstract

In the present study, we investigated whether a mixture of fucoidan and Crepidiastrum denticulatum extract (FCE) had the potential to improve the therapeutic efficacy of cancer treatment. The results demonstrated that FCE significantly reduced cell viability and induced the release of LDH (lactate dehydrogenase) and DNA fragmentation in HepG2 cells in a dose-dependent manner. In addition, FCE treatment also increased the protein expression level of p53, the release of cytochrome c, and the loss of mitochondrial membrane potential. Moreover, FCE dose-dependently increased protein expression levels of Bax, and cleaved caspase-3 and -9. However, FCE decreased the protein expression level of Bcl-2. These results suggest that FCE inhibits cell proliferation and induces apoptosis via the mitochondrial-mediated intrinsic pathway. The present study demonstrates that FCE can be used as an anti-cancer agent for liver cancer based on apoptosis mechanism.

참고문헌 (51)

  1. Ale MT, "Fucose-containing sulfated polysaccharides from brown seaweeds inhibit proliferation of melanoma cells and induce apoptosis by activation of caspase-3 in vitro", Mar Drugs, 9, pp.2605~2621 (2011)
  2. Ahn HR, "Hydroxycinnamic acids in Crepidiastrum denticulatum protect oxidative stress-induced retinal damage", J Agric Food Chem, 62, pp.1310~1323 (2014)
  3. An W, "Apoptotic pathway as the therapeutic target for anticancer traditional Chinese medicines", Front Pharmacol, 10, pp.758~ (2019)
  4. Atashrazm F, "Fucoidan and cancer : A multifunctional molecule with anti-tumor potential", Mar Drugs, 13, pp.2327~2346 (2015)
  5. Chang WC, "Caffeic acid induces apoptosis in human cervical cancer cells through the mitochondrial pathway", Taiwan J Obstet Gynecol, 49, pp.419~424 (2010)
  6. Chao X, "The effects and mechanism of peiminine- induced apoptosis in human hepatocellular carcinoma HepG2 cells", PLoS One, 14, pp.e0201864~ (2019)
  7. Choi H, "Weight change in adulthood and incident risk of cancer", MS, pp.2021
  8. Chuang JY, "Induction of G0", G1 arrest and apoptosis by 3-hydroxycinnamic acid in human cervix epithelial carcinoma(HeLa)cells, 2005, pp.19, 683~688
  9. Fan L, "Silymarin induces cell cycle arrest and apoptosis in ovarian cancer cells", Eur J Pharmacol, 743, pp.79~88 (2014)
  10. Fitton JH, "Therapies from fucoidan: Multifunctional marine polymers", Mar Drugs, 9, pp.1731~1760 (2011)
  11. Fitton JH, "Therapies from fucoidan : An update", Mar Drugs, 13, pp.5920~5946 (2015)
  12. Folin O, "On phosphotungstic-phosphomolybdic compounds as color regents", J Biol Chem, 12, pp.239~243 (1912)
  13. Gao S, "Cepharanthine induces autophagy, apoptosis and cell cycle arrest in breast cancer cells", Cell Physiol Biochem, 41, pp.1633~1648 (2017)
  14. Guo H, "Kaempferol induces apoptosis in HepG2 cells via activation of the endoplasmic reticulum stress pathway", Mol Med Rep, 13, pp.2791~2800 (2016)
  15. Harakeh S, "Apoptosis induction in human hepatoma cell line HepG2 cells by trans-Anethole via activation of mitochondria-mediated apoptotic pathways", Biomed Pharmacother, 165, pp.115236~ (2023)
  16. Ho HY, "Luteolin-7-O-glucoside inhibits cell proliferation and modulates apoptosis through the AKT signaling pathway in human nasopharyngeal carcinoma", Environ Toxicol, 36, pp.2013~2024 (2021)
  17. Kan J, "A Novel combination of wheat peptides and fucoidan attenuates ethanol-induced gastric mucosal damage through anti-oxidant, anti-inflammatory, and pro-survival mechanisms", Nutrients, 9, pp.978~ (2017)
  18. Kaneta M, "Identification of flavones in sixteen Compositae species", Agric Bioi Chem, 42, pp.475~477 (1978)
  19. Kang KS, "Youngia denticulata protects against oxidative damage induced by tert-butylhydroperoxide in HepG2 cells", J Med Food, 14, pp.1198~1207 (2011)
  20. Kawabe T, "G2 checkpoint abrogators as an anticancer drugs", Mol Cancer Ther, 3, pp.513~519 (2004)
  21. Kim BM, "Extract from Artemisia annua Linné induces apoptosis through the mitochondrial signaling pathway in HepG2 cells", J Korean Soc Food Sci Nutr, 45, pp.1708~1716 (2016)
  22. Kim DH, "Reactive oxygen species-mediated phosphorylation of p38 signaling is critically involved in apoptotic effect of Tanshinone I in colon cancer cells", Phytother Res, 32, pp.1975~1982 (2018)
  23. Kim DS, "Ethanol extract of Saussurea lappa root induces apoptosis through an ROS-MAPKs-linked cascade", Yakhak Hoeji, 56, pp.173~179 (2012)
  24. Kim I, "Screening of ethanol extracts of Korean fruits and vegetables for cell viability and antioxidant enzyme activity on alloxan-induced oxidative stress in pancreatic beta cell", J Korean Soc People Plant Environ, 15, pp.85~92 (2012)
  25. Kim JS, "Crepidiastrum denticulatum extract ameliorates kidney ischemia-reperfusion injury in mice", Transplant Proc, 50, pp.1160~1166 (2018)
  26. Kim M, "Youngiasides A and C isolated from Youngia denticulatum inhibit UVB-induced MMP expression and promote type I procollagen production via repression of MAPK", AP-1, Nrf2 in HaCaT cells and human dermal fibroblasts, pp.J Agric Food Chem, 2015[DOI]
  27. Kim MS, "Chicoric acid attenuate a nonalcoholic steatohepatitis by inhibiting key regulators of lipid metabolism, fibrosis, oxidation, and inflammation in mice with methionine and choline deficiency", Mol Nutr Food Res, 61, pp.1600632~ (2017)
  28. Kim SN, "Antioxidant activities and determination of phenolic compounds isolated from oriental plums(soldam, oishiwase and formosa)", Nutr Res Pract, 6, pp.277~285 (2012)
  29. Kong F, "Chinese herbal medicines for prostate cancer therapy : From experimental research to clinical practice", Chin Herb Med, 15, pp.485~495 (2023)
  30. Krylova NV, "In vitro anti-orthohantavirus activity of the high-and low-molecular-weight fractions of fucoidan from the brown alga Fucus evanescens", Mar Drugs, 19, pp.577~ (2021)
  31. Kunnumakkara AB, "Gossypin, a pentahydroxy glucosyl flavone, inhibits the transforming growth factor beta-activated kinase-1-mediated NF-kappaB activation pathway, leading to potentiation of apoptosis, suppression of invasion and abrogation of osteoclastogenesis", Blood, 109, pp.5112~5121 (2007)
  32. Kyung J, "Synergistic anti-inflammatory effects of Laminaria japonica fucoidan and Cistanche tubulosa extract", Lab Anim Res, 28, pp.91~97 (2012)
  33. Lee HJ, "Bioavailability of hydroxycinnamic acids from Crepidiastrum denticulatum using simulated digestion and Caco-2 intestinal cells", J Agric Food Chem, 62, pp.5290~5295 (2014)
  34. Li P, "Cytochrome c and dATP-dependent formation of Apaf-1", caspase-9 complex initiates an apoptotic protease cascade, 1997, pp.91, 479~489
  35. Luiz-Ferreira A, "TRAIL-sensitizing effects of flavonoids in cancer", Int J Mol Sci, 24, pp.16596~ (2023)
  36. Mabate B, "Fucoidan structure and its impact on glucose metabolism : Implications for diabetes and cancer therapy", Mar Drugs, 19, pp.30~ (2021)
  37. Nagamine T, "Inhibitory effect of fucoidan on Huh7 hepatoma cells through downregulation of CXCL12", Nutr Cancer, 61, pp.340~347 (2009)
  38. Park C, "Sagantang-induced apoptotic cell death is associated with the activation of caspases in AGS human gastric carcinoma cells", J Life Sci, 25, pp.1384~1392 (2015)
  39. Qi G, "Athyrium multidentatum(Doll. )Ching extract induce apoptosis via mitochondrial dysfunction and oxidative stress in HepG2 cells", Sci Rep, 7, pp.2275~ (2017)
  40. Riedl SJ, "Structure of the apoptotic protease-activating factor 1 bound to ADP", Nature, 434, pp.926~933 (2005)
  41. Ryu SM, "Anti-proliferative effects and apoptosis induced by chrysin or emodin in human colorectal HCT116 cells", J Life Sci, 31, pp.929~936 (2021)
  42. Senthilkumar K, "Brown seaweed fucoidan : Biological activity and apoptosis, growth signaling mechanism in cancer", Int J Biol Macromol, 60, pp.366~374 (2013)
  43. Song Y, "HO-1089 and HO-1197, novel herbal formulas, have antitumor effects via suppression of PLK1(Polo-like Kinase 1)expression in hepatocellular carcinoma", Cancers(Basel), 15, pp.851~ (2023)
  44. Wang W, "The antiviral activities and mechanisms of marine polysaccharides : An overview", Mar Drugs, 10, pp.2795~2816 (2012)
  45. Wang X, "Chlorogenic acid inhibits proliferation and induces apoptosis in A498 human kidney cancer cells via inactivating PI3K", Akt, J Pharm Pharmacol, pp.2019, 71[DOI]
  46. Yang BK, "Antitumor effects and immunomodulating activities of Phellinus linteus extract in a CT-26 cell-injected colon cancer mouse model", Mycobiology, 37, pp.128~132 (2009)
  47. Yoo JH, "Crepidiastrum denticulatum extract protects the liver against chronic alcohol-induced damage and fat accumulation in rats", J Med Food, 17, pp.432~438 (2014)
  48. Yun JH, "Bi-functional induction of the quinone reductase and cytochrome P450 1A1 by youngiasides via Nrf2-ARE and AhR-XRE pathways", Biol Pharm Bull, 33, pp.1650~1657 (2010)
  49. Yoshida A, "Endonuclease activation and chromosomal DNA fragmentation during apoptosis in leukemia cells", Int J Hematol, 84, pp.31~37 (2006)
  50. Zeng A, "Chlorogenic acid induces apoptosis, inhibits metastasis and improves antitumor immunity in breast cancer via the NF-κB signaling pathway", Oncol Rep, 45, pp.717~727 (2021)
  51. Zhang Z, "Fucoidan extract enhances the anti-cancer activity of chemotherapeutic agents in MDA-MB-231 and MCF-7 breast cancer cells", Mar Drugs, 11, pp.81~98 (2013)

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