Browse > Article
http://dx.doi.org/10.5010/JPB.2010.37.1.057

Autophagy: Noble target mechanisms in natural medicines as anticancer agents  

Kang, Se-Chan (Department of Natural Medicine Resources, Semyung University)
Publication Information
Journal of Plant Biotechnology / v.37, no.1, 2010 , pp. 57-66 More about this Journal
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.
Keywords
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Qadir MA, Kwok B, Dragowska WH, To KH, Le D, Bally MB, Gorski SM (2008) Macroautophgy inhibition sensitizes tamoxifen-resistant breast cancer cells and enhances mitochondrial depolarization, Breast Cancer Res. Treat.
2 Karantza-Wadsworth V, Patel S, Kravchuk O, Chen G, Mathew R, Jin S, White E (2007) Autophagy mitigates metabolic stress and genome damage in mammary tumorigenesis. Genes Dev 21:1621-1635   DOI
3 Nan C, Jayanta D (2010) Autophagy and tumorigenesis. FEBS Letters 1-8
4 Newman DJ, Cragg GD (2007) Natual Products as Sources of New Drug over the Last 25 Years J. Nat. Prod 70:461-477   DOI
5 Pattingre S, Levine B (2006) Bcl-2 inhibition of autophagy: a new route to Cancer? Cancer Res. 66:2885-2888   DOI
6 Levine B, Sinha S, Kroemer G (2008) Bcl-2 family members: dual regulators of apoptosis and autophagy. Autophagy 4:600-606   DOI
7 Kisen GO, Tessitore L, Costelli P, Cordon PB, Schwarze PE, Baccino FM, Seglen PO (1993) Reduced autophagic activity in primary rat hepatocellular carcinoma and ascites hepatoma cells. Carcinogenesis 14:2501-2505   DOI
8 Knecht E, Hernandez YJ, Grisolia S (1984) Regulation of lysosomal autophagy in transformed and non-transformed mouse fibroblasts under several growth conditions. Exp Cell Res 154:224-232   DOI
9 Kwon JY, Cheon SH, Lee HR, Han JY, Kim DI (2009) Production of biopharmaceuticals in transgenic plant cell suspension sultures. J Plant Biotechnol 36:309-319   DOI
10 Liang C, Lee JS, Inn KS, Gack MU, Li Q, Roberts EA, Vergen I, Deretic V, Feng P, Akazawa C, Jung JU (2008) Beclin1-binding UVRAG targets the class C Vps Complex to coordinate autophagosome maturation and endocytic trafficking, Nat. Cell Bio 10:776-787   DOI
11 Liang J, Shao SH, Xu ZX, Hennessy B, Ding Z, Larrea M, Kondo S, Dumont DJ, Gutterman JU, Walker CL, Sligerland JM, Mills GB, (2007) The energy sensing LKB1-AMPK pathway regulates p27(kip 1) phosphorylation mediating the decision to enter autophagy or apoptosis. Net. Cell Biol 9:218-224   DOI
12 Galluzzi L, Vicencio JM, Kepp O, Tasdemir E, Maiurl MC, Kroemer G (2008) To die or not to die: that is the autophagic question. Curr 8:78-91
13 Gozuacik D, Kimchi A (2004) Autophagy as a cell death and tumor suppressor mechanism. Oncogene 23:2891-2906   DOI
14 Gunn JM, Clark MG, Knowles SE, Hopgood MF, Ballard FJ (1977) Reduced rates of proteolysis in transformed cells. Nature 266: 58-60   DOI
15 Mathew R, Kongara S, Beaudoin B, Karp CM, Bray K, Degenhardt K, Chen G, Jin E, White E (2007) Autophagy suppresses tumor progression by limiting chromosomal instability. Genes Dev 21:1367-1381   DOI
16 Morselli E, Tasdemir E, Maiuri MC, GAlluzzi L, Kepp O, criollo A, Vicencio JM, Soussi T, Kroemer G (2008) Mutant p53 protein localized in the cytoplasm inhibits autophagy. Cell Cycle 7:3056-3061   DOI   ScienceOn
17 Greem JR (2003) Antituomor effects of bisphosphonates. Cancer 97:840-7   DOI
18 Green JR (2004) Bisphosphonates: preclinical review. Oncologist 4:3-13
19 Gronostajski RM and Pardee AB (1984) Protein degradation in 3T3 cells and tumorigenic transformed 3T3 cells. J Cell Physiol 119: 127-32   DOI
20 Hamacher-Brady A, Brady NR, Logue SE, Sayen MR, Jinno M Kirshenbaum LA, Gottlieb RA, Gustafsson AB (2007) Response to myocardial ischemia/reperfusion injury involves Bnip3 and autophagy. Cell Death Differ 14:146-157   DOI
21 Harrison B, Kraus M, Burch L, Stevenc C, Craig A, Gordon-Weeks P, Hupp TR (2008) DAPK-1 binding to a linar peptide motif in MAP1B stimulates autophagy and membrane blebbing. J. Biol. Chem 283:9999-1014   DOI
22 Johnstone RW, Ruefli AA, lowe SW (2002) Apoptosis: alink between cancer therapy. Cell 108:153-64   DOI
23 Jonathan R, Green JR (2002) Pharmacologic profile of zoledronic acid: a highly potent inhibitor of bone resorption. Durg Dev Res 55:210-24
24 Daido S, Kanzawa T, Yamamoto A, Takeuchi H, Kondo Y, Kondo S (2004) Pivotal role of the cell death facor BNIP3 in ceramide-induced autophagic cell death in malignant glioma cells. Cancer Res 64:4286-4293   DOI
25 Eugenia M, Lorenzo G, Oliver K, Jose-Miguel V, Algredo C, Maria Chiara M, Guido K (2009) Anti- and pro-tumor functions of autophay. Biochimcal et Biophysica Acts 1793:1524-1532   DOI   ScienceOn
26 Dedenhardt K, Mathew R, Beaudoin B, Bray K, Anderson D, Chen G, Mukherjee C, Shi Y, Gelinas C, Fan Y, Nelson DA, Jin S, White E (2006) Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis. Cancer cell 10:51-64   DOI
27 Degenhardt K, Mathew R, Beaudoin B, Bray K, Anderson D, Chen G, Mukherjee C, Shi Y, Gelinas C, Fan Y, Nelson DA, Jin S, Whtie E (2006) Autophagy promotes tumor cell surval and restricts necrosis, inflammation, and tumorigenesis. Cancer Cell 10:51-64   DOI
28 Edinger AL, Cinalli RM, Thompson CB (2003) Rab7 prevents growth factor independent survival by inhibiting cell-automous nutrient transporter expression. Dev. Cell 5:961-967
29 Festuccia C, Angelucci A, Gravina GL, Biordi L, Millimaggi D, Muzi P, Vicentini C, BoloGna M (2005) Epidermal growth factor modulates prostate cancer cell invasiveness regulating urokinase-type plasminogen activator activity. EGF-receptor inhibition may prevent tumor cell bissemination. Thromb Haemost 93:964-75
30 Fulda S, Debatin KM (2004) Targeting apoptosis pathways in cancer therapy. Curr Cancer Durg Targets 4:569-76   DOI
31 Fulda S, Debatin KM (2006) Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Ocecogene 25:8543-67
32 Barbara MS, David MR, Peter EL, Ilya R (2007) Revisiting the anient concept of botanical therapeutics. NATURE CHEMICAL BIOLOGY 3:360-366   DOI
33 Chen G, Burger MM (2004) p150 overexpression in gastric carcinoma: the addociation with p53. Apopotosis and cell proliferation. Int. J. Cancer 84:95-100
34 Canuto RA, Tessitore L, Muzio G, Autelli R, Baccino FM (1993) Tissue protein turnover during liver carcinogenesis. Carcinogenesis 14:2581-2587   DOI
35 Canuto RA, Tessitore L, Muzio G, Autelli R, Baccino FM, (1993) Tissue protein turnover during liver carcinogenesis. Carcinogenesis 14:2581-7   DOI
36 Carew JS, Nawrocki ST, Kahue CN, Zhang H, Yang C, Chung L, Houghton JA, Huang P, Giles FJ, Cleveland JL (2007) Targeting autophagy auments the anticancer activity of the histone deacetylace inhibitor SAHA to overcome Bcr-Ablmediated drug resistance. Blood 110:313-322   DOI
37 Chen N, Karantza-Wadsworth V (2009) Role and regulation of autophagy in cancer. Biochimica et Biophysica Acta 1793:1516-1523   DOI   ScienceOn
38 Clarke PG (1990) Developmental cell death: morphological diversity and multiple mechanisms. Anat Embryol (Berlin) 181:195-213
39 Cockle SM, Dean RT (1984) 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 221:53-60   DOI
40 Cully M, You H, Levine AJ, Mak TW (2006) Byond PTEN mutations: the PI3K pathway as an integrator of multiple inputs during tumorigenesis. Nat. Rev. Cancer 6:184-192   DOI
41 Allgayer H, Fulda S (2008) An introduction to molecular targeted therapy of cancer. Advances in medical sciences 53:130-138   DOI
42 Abedin MJ, Wang D Mcdonnell MA, Lehmann U, Kelekar A (2007) Autophagy delays apoototic death in breast cancer cells following DNA damage. Cell Death Differ 14:500-510   DOI   ScienceOn
43 Abida WM, Gu W (2008) p53-Dependent and p53-independent activation of autophagy by ARF. Cancer Res 68:352-357   DOI
44 Ahlberg J, Yucel T, Eriksson L, Glaumann H (1987) Characterization of the proteolytic compartment in rat hepatocyte nodules. Virchows Arch B Cell Pathol Incl Mol Pathol 53:79-88   DOI
45 Apel A, Herr I, Schwarz H, Rodemann HP, Mayer A (2008) Blocked autophagy sensitizes resistant carcinoma cells to radiation therapy. Cancer Res 68:1485-1494   DOI
46 Arico S, petiot A, Bauvy C, Dubbelhuis PF, Meijer AJ, Codogno P, Ogier-Denis E (2001) The tumor suppressor PTeN positively regulates macroautophay by inhibiting the phosphatidylinoditol 3-kinase/protein kinase Bpathway. J.Biol, Chem 276:35243-35246   DOI
47 Lu Z, Luo RZ, Lu Y, Zhang X, Yu Q, Khare S, Kondo S, Kondo Y, Yu Y, Mills GB, Liao WS, Bast Jr RC (2008) The tumor suppressor gene ARHI regulates autophagy and tumor dormancy in human ovarian cancer cells. J. Clin invest 118: 3917-3929
48 Marino G, Salvador-Montoliu N, Fueyo A, Knecht E, Mizushima N, Lopezotine C (2007) Tissue-specific autophagy alterations and increased tumorigenesis in mice deficient in Atg4C/ autophagun-3. J.Biol Chem 282:18573-18583   DOI
49 Maiuri MC, Le Toumelin G, Criollo A, Rain JC, Gautier F, Juin P, Tasdemir E, Functional G, Troulinaki K, Tavernarakis N, Hickman JA, Geneste O, Kroemer G (2007) Functional and physical interaction between Bcl-X(L) and a BH30like domain in Belin-1. EMBO J 26:2527-2539   DOI
50 Lopiccolo Y, Blumenthal Gm, Bernstenin WB, Dennis PA (2008) Targeting the PI3K/ Akt/mTOR pathway: effective combinations and clinical considerations, Drug Resist. Updat 11:32-50   DOI
51 Rogers MJ, Grodon S, Benford HL, Coxon FP, Luckman SP, Monkkonen J, Frith JC (2000) Cellular and molecular mechanisms of action of biphosphonates. Cancer 88:2961-78   DOI
52 Lockwood TD, Minassian IA (1982) Protein turnover and proliferation. Failure of SV-3T3 cells to increase lysosomal proteinases, increase protein degradation and cease net protein accumulation. Biochem J 206:251-258   DOI
53 Tasdemir E, Maiuri MC, Galluzzi L, Vitale I, Djavaheri-Mergny M, D’amelio M, Criollo A, Morselli E, Zhu C, Harper F, Nannmark U, Samara C, Pinton P, Szabadkai G, Pierron G, Blomgren K, Tavernarakis N, Codogno P, Cecconi F, Kroemer G (2008) Regulation of autophagy by cytoplsdmic p53. Nat. Cell Biol 25:1025-1040
54 Ueno T, Sato W, horie Y, Komatsu M, Tanida I, Yoshida M, Ohshima S, Mak TW, Watanabe S, Kominami E (2008) Loss of Pten, a tumor suppressor, csuses the strong inhibition of autophagy without affecting LC3 lipidation. Autophagy 4:692-700   DOI
55 Yucel T, Ahlberg J, Glaumann H (1989) Overall proteolysis in perfused and subfractionated chemically induced malignant hepatoma of rat: effects of amino acids. Exp Mol Pathol 50:38-49   DOI
56 Shaw RJ, Cantley LC (2006) PI(3)K and mTOR signaling controls tumour cell growth. Nature 441: 424-430   DOI
57 Takahashi Y, Coppola D, Matsushita N, Cualing HD, Sum M, Sato Y, Liang C, Jung JU, Chenh JQ, Mul JJ, Pledger WJ, Wang HG, (2007) Bif-1 interacts with Beclin 1 through UVRAG and regulates autophagy and tumorigenesis. Net, Cell Biol 9:1142-1151   DOI
58 Schwarze PE and Seglen PO (1985) Reduced autophagic activity, improved protein balance and enhanced in vitro survival of hepatocytes isolated from carcinogen-treated rats Exp Cell Res 157: 15-28   DOI
59 Liu D, Aguirre Ghiso J, Estrada Y, Ossowski L (2002) EGFR is a transducer of the urokinase receptor initiated signal that is required for in vivo growth of a human carcinoma. Cancer Cell 1:445-57   DOI   ScienceOn
60 Reef S, Zalckvar E, Shifman O, Bialik S, Sabanay H, Oren M, Kimchi A (2006) Ashort mitochondrial form of p19ARF induces autophagy and caspase- independent cell death. Mol. Cell 22:463-475   DOI
61 Samaddar JS, Gaddy VT, Duplantier J, Thandavan SP, Shah M, Smith MJ, Browning D, Rawson J, Smith SB, Barrett JT, Schoenlein PV (2008) A role for macroautophagy in protection against 4-hydroxytamoxifen-induced cell death and the dwvwlopment of antiestrogen resistance, Mol. Cancer Ther 7:2977-2987   DOI
62 Schwartz RA, Fernandez G, Kotulska K, Jowiakk S (2007) Tuberous sclerosis complex: advances in diagnosis, genetics, and management. J. Am. Acad. Mermatol 57:189-202   DOI
63 Reef S, Kimchi A(2008) Nucleolar p19ARF, unlike mitochondrial smRFA, is incapable of inducing p53-independent autophagy. Autophagy 4:866-869   DOI
64 Ling XH, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H, Levine B, (1999) Induction of autophagy and inhibiton of tumorigenesis by beline 1. Nature 402:672-676   DOI
65 Ramsey HJiMR, Hayes DN, Fan C, Kozlowski MP, Torrice C, Wu DC, Shimamura T, Prerea SA, Liang MC, Cai D, Naumov GN, Bao L, Contreras CM, Li D, Chen L, Krishnamurthy J, Koivunen J, Chirieac LR, Padera RF, Bronson RT, Lindeman NI, Christiani DC, Lin X, Shapiro GI, Janne PA, Johnson BE, Meyerson M, Kwiatkowski DJ, Castrillon DH, Bardeesy N, Sharpless NE, Wong KK (2007) LKB1 modulates lung cancer differentiation and metastasis. Nature 448: 807-810   DOI
66 Rashmi R, Pillai SG, Vijayalingam S, Ryerse J, Chinnadurai G (2008) BH3-only protein BIK induces caspase-independent cell death with autophagic features in Bcl-2 null cells. Oncogene 27:1366-1375
67 Ling C, Lee JS, Inn KS, Gack MU, Li Q, Roberts EA, Vergne I Deretic V, Feng P, Akazawa C, Jung JU (2008) Beclin1-binding UVRaG targets the class C Vps complex to coordinate autophagosome maturation and endocytic trafficking. Net Cell Biol 10:776-787   DOI