본문 바로가기
KERD
논문KCI 등재

자가식세포작용: 천연물항암제로서의 신규작용기전

Autophagy: Noble target mechanisms in natural medicines as anticancer agents

강세찬
한국식물생명공학회 (Korean Society for Plant Biotechnology)|2010.03|Journal of Plant Biotechnology|제37권 제1호|pp. 57-66

1

조회

0

다운로드

3

인용

0

참고문헌

주제분류농학

초록

Programmed cell death systems are important for an active type of cell deaths. Among them, a type of programmed cell death, autophagy is activated in cancer cells in response to multiple stresses and has been demonstrated to promote tumor cell survival and drug resistance. Thus, in the area of cancer, over the time frame form around the 1940s to date, of the 155 small molecules, 73% are other than “synthetic”, with 47% actually being either “natural products”or “directly derived therefrom”. Autophagy has multiple physiological functions in multicellular organisms, including protein degradation and organelle turnover. Genes and proteins that constitute the basic machinery of the autophagic process were first identified in the yeast system and some of their mammalian orthologues have been characterized as well. Numerous oncogenes, including Akt1, Bcl-2, NF1,PDPK1, class I PI3K, PTEN, and Ras and oncosuppressors,inculuding Bec-1, Bif-1, DAPK-1, p53 and UVRAG suppress or promote the autophagy pathway. Regulation of autophagy in tumors is governed by similar principles of the normal cells, only in a much more complicated manner,given the frequently observed abnormal PI3K activation in cancer and the multitude of interactions between the PI3K/AKT/mTOR pathway and other cell signaling cascades,often also deregulated in tumor cells. Autophagy induction by some anticancer agents underlines the potential utility of its induction as a new cancer treatment modality of development for natural medicines.

Abstract

Programmed cell death systems are important for an active type of cell deaths. Among them, a type of programmed cell death, autophagy is activated in cancer cells in response to multiple stresses and has been demonstrated to promote tumor cell survival and drug resistance. Thus, in the area of cancer, over the time frame form around the 1940s to date, of the 155 small molecules, 73% are other than “synthetic”, with 47% actually being either “natural products”or “directly derived therefrom”. Autophagy has multiple physiological functions in multicellular organisms, including protein degradation and organelle turnover. Genes and proteins that constitute the basic machinery of the autophagic process were first identified in the yeast system and some of their mammalian orthologues have been characterized as well. Numerous oncogenes, including Akt1, Bcl-2, NF1,PDPK1, class I PI3K, PTEN, and Ras and oncosuppressors,inculuding Bec-1, Bif-1, DAPK-1, p53 and UVRAG suppress or promote the autophagy pathway. Regulation of autophagy in tumors is governed by similar principles of the normal cells, only in a much more complicated manner,given the frequently observed abnormal PI3K activation in cancer and the multitude of interactions between the PI3K/AKT/mTOR pathway and other cell signaling cascades,often also deregulated in tumor cells. Autophagy induction by some anticancer agents underlines the potential utility of its induction as a new cancer treatment modality of development for natural medicines.

참고문헌 (67)

  1. Abedin MJ, "Autophagy delays apoototic death in breast cancer cells following DNA damage", Cell Death Differ, 14, pp.500~510 (2007)
  2. Abida WM, "p53-Dependent and p53-independent activation of autophagy by ARF", Cancer Res, 68, pp.352~357 (2008)
  3. Ahlberg J, "Charac terization of the proteolytic compartment in rat hepatocyte nodules", Virchows Arch B Cell Pathol Incl Mol Pathol, 53, pp.79~88 (1987)
  4. Allgayer H, "An introduction to molecular targeted therapy of cancer", Advances in medical sciences, 53, pp.130~138 (2008)
  5. Apel A, "Blocked autophagy sensitizes resistant carcinoma cells to radiation therapy", Cancer Res, 68, pp.1485~1494 (2008)
  6. Arico S, "The tumor suppressor PTeN positively regulates macroautophay by inhibiting the phosphatidylinoditol 3-kinase", protein kinase Bpathway, 2001, pp.276, 35243~35246
  7. Barbara MS, "Revisiting the anient concept of botanical therapeutics", NATURE CHEMICAL BIOLOGY, 3, pp.360~366 (2007)
  8. Canuto RA, "Tissue protein turnover during liver carcinogenesis", Carcinogenesis, 14, pp.2581~2587 (1993)
  9. Canuto RA, "Tissue protein turnover during liver carcinogenesis", Carcinogenesis, 14, pp.2581~2587 (1993)
  10. Carew JS, "Targeting autophagy auments the anticancer activity of the histone deacetylace inhibitor SAHA to overcome Bcr-Ablmediated drug resistance", Blood, 110, pp.313~322 (2007)
  11. Chen G, "p150 overexpression in gastric carcinoma:the addociation with p53. Apopotosis and cell proliferation", Int. J. Cancer, 84, pp.95~100 (2004)
  12. Chen N, "Role and regulation of autophagy in cancer", Biochimica et Biophysica Acta, 1793, pp.1516~1523 (2009)
  13. Clarke PG, "Developmental cell death: morphological diversity and multiple mechanisms", Anat Embryol (Berlin), 181, pp.195~213 (1990)
  14. Cockle SM, "Distinct proteolytic mechanisms in serum-sufficient and serum-restricted fibroblasts. Transformed 3T3 cells fail to regulate proteolysis in relation to culture density only during serum-sufficiency", Biochem J, 221, pp.53~60 (1984)
  15. Cully M, "Byond PTEN mutations: the PI3K pathway as an integrator of multiple inputs during tumorigenesis", Nat. Rev. Cancer, 6, pp.184~192 (2006)
  16. Daido S, "Pivotal role of the cell death facor BNIP3 in ceramide-induced autophagic cell death in malignant glioma cells", Cancer Res, 64, pp.4286~4293 (2004)
  17. Dedenhardt K, "Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis", Cancer cell, 10, pp.51~64 (2006)
  18. Degenhardt K, "Autophagy promotes tumor cell surval and restricts necrosis, inflammation, and tumorigenesis", Cancer Cell, 10, pp.51~64 (2006)
  19. Edinger AL, "Rab7 prevents growth factor independent survival by inhibiting cell-automous nutrient transporter expression", Dev. Cell, 5, pp.961~967 (2003)
  20. Eugenia M, "Anti- and pro-tumor functions of autophay", Biochimcal et Biophysica Acts, 1793, pp.1524~1532 (2009)
  21. Festuccia C, "Epidermal growth factor modulates prostate cancer cell invasiveness regulating urokinase-type plasminogen activator activity. EGF-receptor inhibition may prevent tumor cell bissemination", Thromb Haemost, 93, pp.964~975 (2005)
  22. Fulda S, "Targeting apoptosis pathways in cancer therapy", Curr Cancer Durg Targets, 4, pp.569~576 (2004)
  23. Fulda S, "Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy", Ocecogene, 25, pp.8543~8567 (2006)
  24. Galluzzi L, "To die or not to die: that is the autophagic question", Curr, 8, pp.78~91 (2008)
  25. Gozuacik D, "Autophagy as a cell death and tumor suppressor mechanism", Oncogene, 23, pp.2891~2906 (2004)
  26. Greem JR, "Antituomor effects of bisphosphonates", Cancer, 97, pp.840~847 (2003)
  27. Green JR, "Bisphosphonates: preclinical review", Oncologist, 4, pp.3~13 (2004)
  28. Gronostajski RM, "Protein degradation in 3T3 cells and tumorigenic transformed 3T3 cells", J Cell Physiol, 119, pp.127~132 (1984)
  29. Gunn JM, "Reduced rates of proteolysis in transformed cells", Nature, 266, pp.58~60 (1977)
  30. Hamacher-Brady A, "Response to myocardial ischemia", reperfusion injury involves Bnip3 and autophagy, 2007, pp.14, 146~157
  31. Harrison B, "DAPK-1 binding to a linar peptide motif in MAP1B stimulates autophagy and membrane blebbing", J. Biol. Chem, 283, pp.9999~10014 (2008)
  32. Johnstone RW, "Apoptosis: alink between cancer therapy", Cell, 108, pp.153~164 (2002)
  33. Jonathan R, "Pharmacologic profile of zoledronic acid: a highly potent inhibitor of bone resorption", Durg Dev Res, 55, pp.210~224 (2002)
  34. Karantza-Wadsworth V, "Autophagy mitigates metabolic stress and genome damage in mammary tumorigenesis", Genes Dev, 21, pp.1621~1635 (2007)
  35. Kisen GO, "Reduced autophagic activity in primary rat hepatocellular carcinoma and ascites hepatoma cells", Carcinogenesis, 14, pp.2501~2505 (1993)
  36. Knecht E, "Regulation of lysosomal autophagy in transformed and non-transformed mouse fibroblasts under several growth conditions", Exp Cell Res, 154, pp.224~232 (1984)
  37. 권준영, "형질전환 식물세포배양을 이용한 바이오의약품 생산", Journal of Plant Biotechnology, 36(4), pp.309~319 (2009), 한국식물생명공학회
  38. Levine B, "Bcl-2 family members: dual regulators of apoptosis and autophagy", Autophagy, 4, pp.600~606 (2008)
  39. Liang C, "Beclin1-binding UVRAG targets the class C Vps Complex to coordinate autophagosome maturation and endocytic trafficking", Nat. Cell Bio, 10, pp.776~787 (2008)
  40. Liang J, "The energy sensing LKB1-AMPK pathway regulates p27(kip 1) phosphorylation mediating the decision to enter autophagy or apoptosis", Net. Cell Biol, 9, pp.218~224 (2007)
  41. Ling C, "Beclin1-binding UVRaG targets the class C Vps complex to coordinate autophagosome maturation and endocytic trafficking", Net Cell Biol, 10, pp.776~787 (2008)
  42. Ling XH, "Induction of autophagy and inhibiton of tumorigenesis by beline 1", Nature, 402, pp.672~676 (1999)
  43. Liu D, "EGFR is a transducer of the urokinase receptor initiated signal that is required for in vivo growth of a human carcinoma", Cancer Cell, 1, pp.445~457 (2002)
  44. Lockwood TD, "Protein turnover and proliferation. Failure of SV-3T3 cells to increase lysosomal proteinases, increase protein degradation and cease net protein accumulation", Biochem J, 206, pp.251~258 (1982)
  45. Lopiccolo Y, "Targeting the PI3K", Akt, Drug Resist. Updat, pp.2008, 11[DOI]
  46. Lu Z, "The tumor suppressor gene ARHI regulates autophagy and tumor dormancy in human ovarian cancer cells", J. Clin invest, 118, pp.3917~3929 (2008)
  47. Maiuri MC, "Functional and physical interaction between Bcl-X(L) and a BH30like domain in Belin-1", EMBO J, 26, pp.2527~2539 (2007)
  48. Marino G, "Tissue-specific autophagy alterations and increased tumorigenesis in mice deficient in Atg4C", autophagun-3, 2007, pp.282, 18573~18583
  49. Mathew R, "Autophagy suppresses tumor progression by limiting chromosomal instability", Genes Dev, 21, pp.1367~1381 (2007)
  50. Morselli E, "Mutant p53 protein localized in the cytoplasm inhibits autophagy", Cell Cycle, 7, pp.3056~3061 (2008)
  51. Nan C, "Autophagy and tumorigenesis", FEBS Letters, 34, pp.1~8 (2010)
  52. Newman DJ, "Natual Products as Sources of New Drug over the Last 25 Years", J. Nat. Prod, 70, pp.461~477 (2007)
  53. Pattingre S, "Bcl-2 inhibition of autophagy: a new route to Cancer?", Cancer Res., 66, pp.2885~2888 (2006)
  54. Qadir MA, "Macroautophgy inhibition sensitizes tamoxifen-resistant breast cancer cells and enhances mitochondrial depolarization", Breast Cancer Res. Treat, 45, pp.58~69 (2008)
  55. Ramsey HJiMR, "LKB1 modulates lung cancer differentiation and metastasis", Nature, 448, pp.807~810 (2007)
  56. Rashmi R, "BH3-only protein BIK induces caspase-independent cell death with autophagic features in Bcl-2 null cells", Oncogene, 27, pp.1366~1375 (2008)
  57. Reef S, "Nucleolar p19ARF, unlike mitochondrial smRFA, is incapable of inducing p53-independent autophagy", Autophagy, 4, pp.866~869 (2008)
  58. Reef S, "Ashort mitochondrial form of p19ARF induces autophagy and caspase- independent cell death", Mol. Cell, 22, pp.463~475 (2006)
  59. Rogers MJ, "Cellular and molecular mechanisms of action of biphosphonates", Cancer, 88, pp.2961~2978 (2000)
  60. Samaddar JS, "A role for macroautophagy in protection against 4-hydroxytamoxifen-induced cell death and the dwvwlopment of antiestrogen resistance", Mol. Cancer Ther, 7, pp.2977~2987 (2008)
  61. Schwartz RA, "Tuberous sclerosis complex: advances in diagnosis, genetics, and management", J. Am. Acad. Mermatol, 57, pp.189~202 (2007)
  62. Schwarze PE, "Reduced autophagic activity, improved protein balance and enhanced in vitro survival of hepatocytes isolated from carcinogen-treated rats", Exp Cell Res, 157, pp.15~28 (1985)
  63. Shaw RJ, "PI(3)K and mTOR signaling controls tumour cell growth", Nature, 441, pp.424~430 (2006)
  64. Takahashi Y, "Bif-1 interacts with Beclin 1 through UVRAG and regulates autophagy and tumorigenesis", Net, Cell Biol, 9, pp.1142~1151 (2007)
  65. Tasdemir E, "Regulation of autophagy by cytoplsdmic p53", Nat. Cell Biol, 25, pp.1025~1040 (2008)
  66. Ueno T, "Loss of Pten, a tumor suppressor, csuses the strong inhibition of autophagy without affecting LC3 lipidation", Autophagy, 4, pp.692~700 (2008)
  67. Yucel T, "Overall proteolysis in perfused and subfractionated chemically induced malignant hepatoma of rat: effects of amino acids", Exp Mol Pathol, 50, pp.38~49 (1989)

관련 논문AI추천

Induction of cytoprotective autophagy by morusin via AMP-activated protein kinase activation in human non-small cell lung cancer cellsPark Hyun-Ji, Park Shin-Hyung한국영양학회 · Nutrition Research and Practice2020 · 제14권 제5호Celastrol inhibits gastric cancer growth by induction of apoptosis and autophagy이현우, 전경희, 정재호, 조아라, 최혜지, Kenny Seung Bin Jang생화학분자생물학회 · BMB Reports2014 · 제47권 제12호Blockage of Autophagy Rescues the Dual PI3K/mTOR Inhibitor BEZ235- induced Growth Inhibition of Colorectal Cancer Cells박덕배, 오일중, 이영기, 이용훈, 조현철, 천민석한국발생생물학회 · 발생과 생식2016 · 제20권 제1호Naesohwangryeon-tang Induced Apoptosis and Autophagy in A549 Human Lung Cancer Cells박철, 김홍재, 정진우, 최영현, 홍수현대한약침학회 · Journal of Pharmacopuncture2019 · 제22권 제4호桔梗에 의한 NCI-H460 인체 비소세포폐암 세포에서의 autophagy 및 apoptosis 유발 효과박철, 박상은, 최영현, 한민호, 홍상훈, 홍수현대한한방내과학회 · 대한한방내과학회지2014 · 제35권 제3호Ginsenoside Rg1 Induces Autophagy in Colorectal Cancer through Inhibition of the Akt/mTOR/p70S6K PathwayCui Li, Li Lingchang, Lin Lin, Liu Ruiqi, Zhang Bin, Zou Shuting한국미생물·생명공학회 · Journal of Microbiology and Biotechnology2024 · 제34권 제4호

이 간행물의 다른 논문 (12건)

화훼작물의 향기 성분 증대를 위한 대사 공학이긍표, 박천호, 류소영, 서상규, 강승원pp. 1-11식물대사체 연구의 현황과 전망유장렬, 김종현, 권용국, 김석원pp. 12-24바이오디젤 원료작물의 기름 및 지방산 특성에 따른 활용방안 고찰장영석, 김광수, 이영화, 조현준, 서세정pp. 25-46비타민나무의 약리 효과 및 구성 성분유창연, 김주성, 김명조pp. 47-56Output traits in crop plants: Nutrients and pharmaceuticals유주경pp. 67-71
원문 보기