4,018
Views
87
CrossRef citations to date
0
Altmetric
BASIC RESEARCH PAPERS

Elaiophylin, a novel autophagy inhibitor, exerts antitumor activity as a single agent in ovarian cancer cells

, , , , , , , , , , , , , & show all
Pages 1849-1863 | Received 22 May 2014, Accepted 12 Jan 2015, Published online: 27 Oct 2015

References

  • Jayson GC, Kohn EC, Kitchener HC, Ledermann JA. Ovarian cancer. Lancet 2014; 384:1376-88; PMID:24767708; http://dx.doi.org/10.1016/S0140-6736(13)62146-7
  • Bast RC Jr, Hennessy B, Mills GB. The biology of ovarian cancer: new opportunities for translation. Nat Rev Cancer 2009; 9:415-28; PMID:19461667; http://dx.doi.org/10.1038/nrc2644
  • Vaughan S, Coward JI, Bast RC Jr, Berchuck A, Berek JS, Brenton JD, Coukos G, Crum CC, Drapkin R, Etemadmoghadam D, et al. Rethinking ovarian cancer: recommendations for improving outcomes. Nat Rev Cancer 2011; 11:719-25; PMID:21941283; http://dx.doi.org/10.1038/nrc3144
  • Peracchio C, Alabiso O, Valente G, Isidoro C. Involvement of autophagy in ovarian cancer: a working hypothesis. J Ovarian Res 2012; 5:22; PMID:22974323; http://dx.doi.org/10.1186/1757-2215-5-22
  • Orfanelli T, Jeong JM, Doulaveris G, Holcomb K, Witkin SS. Involvement of autophagy in cervical, endometrial and ovarian cancer. Int J Cancer J Int du Cancer 2014; 135:519-28; PMID:24122662; http://dx.doi.org/10.1002/ijc.28524
  • Wang J, Wu GS. Role of autophagy in cisplatin resistance in ovarian cancer cells. J Biol Chem 2014; 289:17163-73; PMID:24794870; http://dx.doi.org/10.1074/jbc.M114.558288
  • Klionsky DJ, Abdalla FC, Abeliovich H, Abraham RT, Acevedo-Arozena A, Adeli K, Agholme L, Agnello M, Agostinis P, Aguirre-Ghiso JA, et al. Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy 2012; 8:445-544; PMID:22966490; http://dx.doi.org/10.4161/auto.19496
  • Mizushima N, Levine B, Cuervo AM, Klionsky DJ. Autophagy fights disease through cellular self-digestion. Nature 2008; 451:1069-75; PMID:18305538; http://dx.doi.org/10.1038/nature06639
  • Mizushima N, Yoshimori T, Levine B. Methods in mammalian autophagy research. Cell 2010; 140:313-26; PMID:20144757; http://dx.doi.org/10.1016/j.cell.2010.01.028
  • Zhang N, Qi Y, Wadham C, Wang L, Warren A, Di W, Xia P. FTY720 induces necrotic cell death and autophagy in ovarian cancer cells: a protective role of autophagy. Autophagy 2010; 6:1157-67; PMID:20935520; http://dx.doi.org/10.4161/auto.6.8.13614
  • Zhu K, Dunner K Jr, McConkey DJ. Proteasome inhibitors activate autophagy as a cytoprotective response in human prostate cancer cells. Oncogene 2010; 29:451-62; PMID:19881538; http://dx.doi.org/10.1038/onc.2009.343
  • Ganley IG, Wong PM, Gammoh N, Jiang X. Distinct autophagosomal-lysosomal fusion mechanism revealed by thapsigargin-induced autophagy arrest. Mol Cell 2011; 42:731-43; PMID:21700220; http://dx.doi.org/10.1016/j.molcel.2011.04.024
  • Gonzalez P, Mader I, Tchoghandjian A, Enzenmuller S, Cristofanon S, Basit F, Debatin KM, Fulda S. Impairment of lysosomal integrity by B10, a glycosylated derivative of betulinic acid, leads to lysosomal cell death and converts autophagy into a detrimental process. Cell Death Differ 2012; 19:1337-46; PMID:22343715; http://dx.doi.org/10.1038/cdd.2012.10
  • McAfee Q, Zhang Z, Samanta A, Levi SM, Ma XH, Piao S, Lynch JP, Uehara T, Sepulveda AR, Davis LE, et al. Autophagy inhibitor Lys05 has single-agent antitumor activity and reproduces the phenotype of a genetic autophagy deficiency. Proc Natl Acad Sci U S A 2012; 109:8253-8; PMID:22566612; http://dx.doi.org/10.1073/pnas.1118193109
  • Voss V, Senft C, Lang V, Ronellenfitsch MW, Steinbach JP, Seifert V, Kögel D. The pan-Bcl-2 inhibitor (-)-gossypol triggers autophagic cell death in malignant glioma. Mol Cancer Res: MCR 2010; 8:1002-16; PMID:20587533; http://dx.doi.org/10.1158/1541-7786.MCR-09-0562
  • Tormo D, Checinska A, Alonso-Curbelo D, Perez-Guijarro E, Canon E, Riveiro-Falkenbach E, Calvo TG, Larribere L, Megías D, Mulero F, et al. Targeted activation of innate immunity for therapeutic induction of autophagy and apoptosis in melanoma cells. Cancer cell 2009; 16:103-14; PMID:19647221; http://dx.doi.org/10.1016/j.ccr.2009.07.004
  • Arai M. Azalomycins B and F, two new antibiotics. I. Production and isolation. J Antibiot 1960; 13:46-50; PMID:13848830
  • Wu Y, Wang X, Guo H, Zhang B, Zhang XB, Shi ZJ, Yu L. Synthesis and screening of 3-MA derivatives for autophagy inhibitors. Autophagy 2013; 9:595-603; PMID:23412639; http://dx.doi.org/10.4161/auto.23641
  • Pankiv S, Clausen TH, Lamark T, Brech A, Bruun JA, Outzen H, Øvervatn A, Bjørkøy G, Johansen T. p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J Biol Chem 2007; 282:24131-45; PMID:17580304; http://dx.doi.org/10.1074/jbc.M702824200
  • Kawai A, Uchiyama H, Takano S, Nakamura N, Ohkuma S. Autophagosome-lysosome fusion depends on the pH in acidic compartments in CHO cells. Autophagy 2007; 3:154-7; PMID:17204842; http://dx.doi.org/10.4161/auto.3634
  • Vazquez CL, Colombo MI. Assays to assess autophagy induction and fusion of autophagic vacuoles with a degradative compartment, using monodansylcadaverine (MDC) and DQ-BSA. Methods Enzymol 2009; 452:85-95; PMID:19200877; http://dx.doi.org/10.1016/S0076-6879(08)03606-9
  • Behrends C, Sowa ME, Gygi SP, Harper JW. Network organization of the human autophagy system. Nature 2010; 466:68-76; PMID:20562859; http://dx.doi.org/10.1038/nature09204
  • Cadwell K, Liu JY, Brown SL, Miyoshi H, Loh J, Lennerz JK, Kishi C, Kc W, Carrero JA, Hunt S, et al. A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells. Nature 2008; 456:259-63; PMID:18849966; http://dx.doi.org/10.1038/nature07416
  • Baek KH, Park J, Shin I. Autophagy-regulating small molecules and their therapeutic applications. Chem Soc Rev 2012; 41:3245-63; PMID:22293658; http://dx.doi.org/10.1039/c2cs15328a
  • Hoyer-Hansen M, Jaattela M. Autophagy: an emerging target for cancer therapy. Autophagy 2008; 4:574-80; PMID:18362515; http://dx.doi.org/10.4161/auto.5921
  • Janku F, McConkey DJ, Hong DS, Kurzrock R. Autophagy as a target for anticancer therapy. Nat Rev Clin Oncol 2011; 8:528-39; PMID:21587219; http://dx.doi.org/10.1038/nrclinonc.2011.71
  • Fiedler HP, Worner W, Zahner H, Kaiser HP, Keller-Schierlein W, Muller A. Metabolic products of microorganisms. 200 Isolation and characterization of niphithricins A, B, and elaiophylin, antibiotics produced by Streptomyces violaceoniger. J Antibiot 1981; 34:1107-18; PMID:7035426; http://dx.doi.org/10.7164/antibiotics.34.1107
  • Haydock SF, Mironenko T, Ghoorahoo HI, Leadlay PF. The putative elaiophylin biosynthetic gene cluster in Streptomyces sp. DSM4137 is adjacent to genes encoding adenosylcobalamin-dependent methylmalonyl CoA mutase and to genes for synthesis of cobalamin. J Biotechnol 2004; 113:55-68; PMID:15380647; http://dx.doi.org/10.1016/j.jbiotec.2004.03.022
  • Drose S, Bindseil KU, Bowman EJ, Siebers A, Zeeck A, Altendorf K. Inhibitory effect of modified bafilomycins and concanamycins on P- and V-type adenosinetriphosphatases. Biochemistry 1993; 32:3902-6; PMID:8385991; http://dx.doi.org/10.1021/bi00066a008
  • Yang YP, Hu LF, Zheng HF, Mao CJ, Hu WD, Xiong KP, Wang F, Liu CF. Application and interpretation of current autophagy inhibitors and activators. Acta Pharmacol Sinica 2013; 34:625-35; PMID:23524572; http://dx.doi.org/10.1038/aps.2013.5
  • Yang ZJ, Chee CE, Huang S, Sinicrope FA. The role of autophagy in cancer: therapeutic implications. Mol Cancer Therap 2011; 10:1533-41; PMID:21878654; http://dx.doi.org/10.1158/1535-7163.MCT-11-0047
  • Blommaart EF, Krause U, Schellens JP, Vreeling-Sindelarova H, Meijer AJ. The phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002 inhibit autophagy in isolated rat hepatocytes. Eur J Biochem/FEBS 1997; 243:240-6; PMID:9030745; http://dx.doi.org/10.1111/j.1432-1033.1997.0240a.x
  • Wu YT, Tan HL, Shui G, Bauvy C, Huang Q, Wenk MR, Ong CN, Codogno P, Shen HM. Dual role of 3-methyladenine in modulation of autophagy via different temporal patterns of inhibition on class I and III phosphoinositide 3-kinase. J Biol Chem 2010; 285:10850-61; PMID:20123989; http://dx.doi.org/10.1074/jbc.M109.080796
  • Rubinsztein DC, Gestwicki JE, Murphy LO, Klionsky DJ. Potential therapeutic applications of autophagy. Nat Rev Drug Disc 2007; 6:304-12; PMID:17396135; http://dx.doi.org/10.1038/nrd2272
  • Geng Y, Kohli L, Klocke BJ, Roth KA. Chloroquine-induced autophagic vacuole accumulation and cell death in glioma cells is p53 independent. Neuro-oncology 2010; 12:473-81; PMID:20406898; http://dx.doi.org/10.1093/neuonc/nop048
  • Amaravadi RK, Yu D, Lum JJ, Bui T, Christophorou MA, Evan GI, Thomas-Tikhonenko A, Thompson CB. Autophagy inhibition enhances therapy-induced apoptosis in a Myc-induced model of lymphoma. J Clin Investigat 2007; 117:326-36; PMID:17235397; http://dx.doi.org/10.1172/JCI28833
  • Rao R, Balusu R, Fiskus W, Mudunuru U, Venkannagari S, Chauhan L, Smith JE, Hembruff SL, Ha K, Atadja P, et al. Combination of pan-histone deacetylase inhibitor and autophagy inhibitor exerts superior efficacy against triple-negative human breast cancer cells. Mol Cancer Therap 2012; 11:973-83; PMID:22367781; http://dx.doi.org/10.1158/1535-7163.MCT-11-0979
  • Rosenfeld MR, Ye X, Supko JG, Desideri S, Grossman SA, Brem S, Mikkelson T, Wang D, Chang YC, Hu J, et al. A phase I/II trial of hydroxychloroquine in conjunction with radiation therapy and concurrent and adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme. Autophagy 2014; 10:1359-68; PMID:24991840; http://dx.doi.org/10.4161/auto.28984
  • Rangwala R, Chang YC, Hu J, Algazy KM, Evans TL, Fecher LA, Schuchter LM, Torigian DA, Panosian JT, Troxel AB, et al. Combined MTOR and autophagy inhibition: phase I trial of hydroxychloroquine and temsirolimus in patients with advanced solid tumors and melanoma. Autophagy 2014; 10:1391-402; PMID:24991838; http://dx.doi.org/10.4161/auto.29119
  • Rangwala R, Leone R, Chang YC, Fecher LA, Schuchter LM, Kramer A, Tan KS, Heitjan DF, Rodgers G, Gallagher M, et al. Phase I trial of hydroxychloroquine with dose-intense temozolomide in patients with advanced solid tumors and melanoma. Autophagy 2014; 10:1369-79; PMID:24991839; http://dx.doi.org/10.4161/auto.29118
  • Goodall ML, Wang T, Martin KR, Kortus MG, Kauffman AL, Trent JM, Gately S, MacKeigan JP. Development of potent autophagy inhibitors that sensitize oncogenic BRAF V600E mutant melanoma tumor cells to vemurafenib. Autophagy 2014; 10:1120-36; PMID:24879157; http://dx.doi.org/10.4161/auto.28594
  • Boya P, Kroemer G. Lysosomal membrane permeabilization in cell death. Oncogene 2008; 27:6434-51; PMID:18955971; http://dx.doi.org/10.1038/onc.2008.310
  • Repnik U, Hafner Cesen M, Turk B. Lysosomal membrane permeabilization in cell death: concepts and challenges. Mitochondrion 2014; PMID:24984038; http://dx.doi.org/10.1016/j.mito.2014.06.006
  • Degtyarev M, De Maziere A, Orr C, Lin J, Lee BB, Tien JY, Prior WW, van Dijk S, Wu H, Gray DC, et al. Akt inhibition promotes autophagy and sensitizes PTEN-null tumors to lysosomotropic agents. J Cell Biol 2008; 183:101-16; PMID:18838554; http://dx.doi.org/10.1083/jcb.200801099
  • Morgan MJ, Gamez G, Menke C, Hernandez A, Thorburn J, Gidan F, Staskiewicz L, Morgan S, Cummings C, Maycotte P, et al. Regulation of autophagy and chloroquine sensitivity by oncogenic RAS in vitro is context-dependent. Autophagy 2014; 10:1814-26; PMID:25136801; http://dx.doi.org/10.4161/auto.32135
  • Rouschop KM, van den Beucken T, Dubois L, Niessen H, Bussink J, Savelkouls K, Keulers T, Mujcic H, Landuyt W, Voncken JW, et al. The unfolded protein response protects human tumor cells during hypoxia through regulation of the autophagy genes MAP1LC3B and ATG5. J Clin Investigat2010; 120:127-41; PMID:20038797; http://dx.doi.org/10.1172/JCI40027
  • Du J, Sun B, Zhao X, Gu Q, Dong X, Mo J, Sun T, Wang J, Sun R, Liu Y. Hypoxia promotes vasculogenic mimicry formation by inducing epithelial-mesenchymal transition in ovarian carcinoma. Gynecol Oncol 2014; 133:575-83; PMID:24589413; http://dx.doi.org/10.1016/j.ygyno.2014.02.034
  • Horiuchi A, Hayashi T, Kikuchi N, Hayashi A, Fuseya C, Shiozawa T, Konishi I. Hypoxia upregulates ovarian cancer invasiveness via the binding of HIF-1alpha to a hypoxia-induced, methylation-free hypoxia response element of S100A4 gene. Int J Cancer J Int du Cancer 2012; 131:1755-67; PMID:22287060; http://dx.doi.org/10.1002/ijc.27448
  • Selvendiran K, Bratasz A, Kuppusamy ML, Tazi MF, Rivera BK, Kuppusamy P. Hypoxia induces chemoresistance in ovarian cancer cells by activation of signal transducer and activator of transcription 3. Int J Cancer J Int du Cancer 2009; 125:2198-204; PMID:19623660; http://dx.doi.org/10.1002/ijc.24601
  • Liang D, Ma Y, Liu J, Trope CG, Holm R, Nesland JM, Suo Z. The hypoxic microenvironment upgrades stem-like properties of ovarian cancer cells. BMC Cancer 2012; 12:201; PMID:22642602; http://dx.doi.org/10.1186/1471-2407-12-201
  • Mazure NM, Pouyssegur J. Hypoxia-induced autophagy: cell death or cell survival? Curr Opin Cell Biol 2010; 22:177-80; PMID:20022734; http://dx.doi.org/10.1016/j.ceb.2009.11.015
  • Hu YL, DeLay M, Jahangiri A, Molinaro AM, Rose SD, Carbonell WS, Aghi MK. Hypoxia-induced autophagy promotes tumor cell survival and adaptation to antiangiogenic treatment in glioblastoma. Cancer Res 2012; 72:1773-83; PMID:22447568; http://dx.doi.org/10.1158/0008-5472.CAN-11-3831
  • Amaravadi RK. Autophagy-induced tumor dormancy in ovarian cancer. J Clin Investigat 2008; 118:3837-40; PMID:19033653; http://dx.doi.org/10.1172/JCI37667
  • Lu Z, Luo RZ, Lu Y, Zhang X, Yu Q, Khare S, Kondo S, Kondo Y, Yu Y, Mills GB, et al. The tumor suppressor gene ARHI regulates autophagy and tumor dormancy in human ovarian cancer cells. J Clin Investigat 2008; 118:3917-29; PMID:19033662; http://dx.doi.org/10.1172/JCI35512
  • Asselin E, Mills GB, Tsang BK. XIAP regulates Akt activity and caspase-3-dependent cleavage during cisplatin-induced apoptosis in human ovarian epithelial cancer cells. Cancer Res 2001; 61:1862-8; PMID:11280739
  • Traganos F, Darzynkiewicz Z. Lysosomal proton pump activity: supravital cell staining with acridine orange differentiates leukocyte subpopulations. Methods Cell Biol 1994; 41:185-94; PMID:7532261; http://dx.doi.org/10.1016/S0091-679X(08)61717-3
  • Liu R, Li J, Zhang T, Zou L, Chen Y, Wang K, Lei Y, Yuan K, Li Y, Lan J, et al. Itraconazole suppresses the growth of glioblastoma through induction of autophagy: involvement of abnormal cholesterol trafficking. Autophagy 2014; 10:1241-55; PMID:24905460; http://dx.doi.org/10.4161/auto.28912

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.