Targeting malignant mitochondria with therapeutic peptides

Therapeutic Delivery

Volumn 3, Issue 8, 2012, Pages 961-979

  Constance, Jonathan E ^a   Lim, Carol S ^a  

^a UNIVERSITY OF UTAH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 [N (GLUTATHIONYLACETYL)AMINO]PHENYLARSENOXIDE; 4 [N (PENICILLAMINYLACETYL)AMINO]PHENYLARSONOUS ACID; ABELSON KINASE; BIFUNCTIONAL HER2 BLOCKING AND APOPTOSIS INDUCING PEPTIDE; HEAT SHOCK PROTEIN 90; HYBRID PROTEIN; INOSITOL 1,4,5 TRISPHOSPHATE RECEPTOR DECOY PEPTIDE; LUTEINIZING HORMONE RELEASING HORMONE PROTEIN BH3 FUSION PROTEIN; MANGANESE SUPEROXIDE DISMUTASE; MITOCHONDRIAL DNA; MITOCHONDRIAL PROTEIN; PENETRATIN PROTEIN BH3 FUSION PROTEIN; PHOSPHOINOSITIDE DEPENDENT PROTEIN KINASE 1; PROTEIN BCL 2; PROTEIN MTCH2; PROTEIN P53; PROTEIN TRAP 1; REACTIVE OXYGEN METABOLITE; SHEPHERDIN; STABILIZED ALPHA HELICES OF BCL 2 FAMILY PROTEIN; SYNTHETIC PEPTIDE; TAT PROTEIN FRAGILE HISTIDINE TRIAD FUSION PROTEIN; TRANSACTIVATOR PROTEIN; UNCLASSIFIED DRUG; VOLTAGE DEPENDENT ANION CHANNEL DECOY PEPTIDE; VPR PROTEIN;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; CARCINOGENICITY; CHANNEL GATING; DRUG CYTOTOXICITY; DRUG TARGETING; GENE SWITCHING; HUMAN; IMMUNOGENICITY; MITOCHONDRIAL MEMBRANE; MITOCHONDRIAL MEMBRANE POTENTIAL; MITOCHONDRIAL PERMEABILITY; MITOCHONDRION; NONHUMAN; PEPTIDE ANALYSIS; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; PROTEIN TARGETING; REVIEW;

EID: 84865510296     PISSN: 20415990     EISSN: 20416008     Source Type: Journal    
DOI: 10.4155/tde.12.75     Document Type: Review

References (157)

1. Ralph SJ, Rodriguez-Enriquez S, Neuzil J, Saavedra E, Moreno-Sanchez R. The causes of cancer revisited: "mitochondrial malignancy" and ROS-induced oncogenic transformation - why mitochondria are targets for cancer therapy. Mol. Aspects Med. 31(2), 145-170 (2010). Comprehensive review of the reciprocal role between mitochondria and oncogenic transformation.
2. McCarty MF. Targeting multiple signaling pathways as a strategy for managing prostate cancer: multifocal signal modulation therapy. Integr. Cancer Ther. 3(4), 349-380 (2004). (Pubitemid 39552429)
3. Mahato RI, Narang AS, Thoma L, Miller DD. Emerging trends in oral delivery of peptide and protein drugs. Crit. Rev. Ther. Drug Carrier Syst. 20(2-3), 153-214 (2003). (Pubitemid 37237279)
4. Tan ML, Choong PF, Dass CR. Recent developments in liposomes, microparticles and nanoparticles for protein and peptide drug delivery. Peptides 31(1), 184-193 (2010).
5. Green DR, Ferguson T, Zitvogel L, Kroemer G. Immunogenic and tolerogenic cell death. Nat. Rev. Immunol. 9(5), 353-363 (2009).
6. Ieva E, Trapani A, Cioffi N, Ditaranto N, Monopoli A, Sabbatini L. Analytical characterization of chitosan nanoparticles for peptide drug delivery applications. Anal. Bioanal. Chem. 393(1), 207-215 (2009). (Pubitemid 50316506)
7. Torchilin VP. Tat peptide-mediated intracellular delivery of pharmaceutical nanocarriers. Adv. Drug Deliv. Rev. 60(4-5), 548-558 (2008). (Pubitemid 351215572)
8. Martins I, Michaud M, Sukkurwala AQ et al. Premortem autophagy determines the immunogenicity of chemotherapy-induced cancer cell death. Autophagy 8 (3) (2012) (Epub ahead of print).
9. Gogvadze V, Zhivotovsky B, Orrenius S. The warburg effect and mitochondrial stability in cancer cells. Mol. Aspects Med. 31(1), 60-74 (2010).
10. Wemeau M, Kepp O, Tesniere A et al. Calreticulin exposure on malignant blasts predicts a cellular anticancer immune response in patients with acute myeloid leukemia. Cell Death Dis. 1, e104 (2010).
11. Bitler BG, Schroeder JA. Anti-cancer therapies that utilize cell penetrating peptides. Recent Pat. Anticancer Drug Discov. 5(2), 99-108 (2010).
12. Fulda S, Galluzzi L, Kroemer G. Targeting mitochondria for cancer therapy. Nat. Rev. Drug Discov. 9(6), 447-464 (2010). Comprehensive review of small molecules targeted to the mitochondria for cancer therapy.
13. Hortobagyi GN. Trastuzumab in the treatment of breast cancer. N. Engl. J. Med. 353(16), 1734-1736 (2005). (Pubitemid 41464714)
14. Nakase I, Konishi Y, Ueda M, Saji H, Futaki S. Accumulation of arginine-rich cellpenetrating peptides in tumors and the potential for anticancer drug delivery in vivo. J. Control. Release 159(2), 181-188 (2012).
15. Christofk HR, Vander Heiden MG, Harris MH et al. The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature 452(7184), 230-233 (2008). Key example of isoform switching of a mitochondrial protein and implications in cancer. (Pubitemid 351380249)
16. Mossalam M, Dixon AS, Lim CS. Controlling subcellular delivery to optimize therapeutic effect. Therapeutic Delivery 1(1), 169-193 (2010).
17. Seyfried TN, Shelton LM. Cancer as a metabolic disease. Nutr. Metab. (Lond.). 27(7), 7 (2010).
18. Chonghaile TN, Sarosiek KA, Vo TT et al. Pretreatment mitochondrial priming correlates with clinical response to cytotoxic chemotherapy. Science 334(6059), 1129-1133 (2011). Provides insight into the role of the Bcl-2 family in the control over cell death in cancer chemotherapeutic responses.
19. Galluzzi L, Kroemer G. Necroptosis: a specialized pathway of programmed necrosis. Cell 135(7), 1161-1163 (2008).
20. Atay C, Ugurlu S, Ozoren N. Shock the heat shock network. J. Clin. Invest. 119(3), 445-448 (2009).
21. Martinou JC, Youle RJ. Mitochondria in apoptosis: Bcl-2 family members and mitochondrial dynamics. Dev. Cell 21(1), 92-101 (2011). Provides insight into the connection between mitochondrial morphological dynamics and the Bcl-2 family proteins.
22. Chipuk JE, Kuwana T, Bouchier-Hayes L et al. Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science 303(5660), 1010-1014 (2004). (Pubitemid 38209704)
23. Kutuk O, Letai A. Regulation of Bcl-2 family proteins by posttranslational modifications. Curr. Mol. Med. 8(2), 102-118 (2008). (Pubitemid 351516830)
24. Szabo I, Soddemann M, Leanza L, Zoratti M, Gulbins E. Single-point mutations of a lysine residue change function of Bax and Bcl-xL expressed in Bax-and Bak-less mouse embryonic fibroblasts: novel insights into the molecular mechanisms of Bax-induced apoptosis. Cell Death Differ. 18(3), 427-438 (2011). Provides a mechanistic connection between mitochondrial potassium channels and the pro-apoptotic protein Bax.
25. Szabo I, Bock J, Grassme H et al. Mitochondrial potassium channel Kv1.3 mediates Bax-induced apoptosis in lymphocytes. Proc. Natl Acad. Sci. USA 105(39), 14861-14866 (2008).
26. Cipolat S, Rudka T, Hartmann D et al. Mitochondrial rhomboid PARL regulates cytochrome c release during apoptosis via OPA1-dependent cristae remodeling. Cell 126(1), 163-175 (2006).
27. Liu T, Hannafon B, Gill L, Kelly W, Benbrook D. Flex-Hets differentially induce apoptosis in cancer over normal cells by directly targeting mitochondria. Mol. Cancer Ther. 6(6), 1814-1822 (2007). (Pubitemid 46954058)
28. Griffin C, Karnik A, McNulty J, Pandey S. Pancratistatin selectively targets cancer cell mitochondria and reduces growth of human colon tumor xenografts. Mol. Cancer Ther. 10(1), 57-68 (2011).
29. Vella S, Conti M, Tasso R, Cancedda R, Pagano A. Dichloroacetate inhibits neuroblastoma growth by specifically acting against malignant undifferentiated cells. Int. J. Cancer 130(7), 1484-1493 (2012).
30. Bellance N, Lestienne P, Rossignol R. Mitochondria: from bioenergetics to the metabolic regulation of carcinogenesis. Front. Biosci. 14, 4015-4034 (2009).
31. Gupta SC, Hevia D, Patchva S, Park B, Koh W, Aggarwal BB. Upsides and downsides of reactive oxygen species for cancer: the roles of reactive oxygen species in tumorigenesis, prevention, and therapy. Antioxid. Redox Signal. 16(11), 1295-1322 (2012).
32. Diehn M, Cho RW, Lobo NA et al. Association of reactive oxygen species levels and radioresistance in cancer stem cells. Nature 458(7239), 780-783 (2009).
33. Ishikawa K, Takenaga K, Akimoto M et al. ROS-generating mitochondrial DNA mutations can regulate tumor cell metastasis. Science 320(5876), 661-664 (2008). (Pubitemid 351928347)
34. Bair JS, Palchaudhuri R, Hergenrother PJ. Chemistry and biology of deoxynyboquinone, a potent inducer of cancer cell death. J. Am. Chem. Soc. 132(15), 5469-5478 (2010).
35. Atlante A, Calissano P, Bobba A, Azzariti A, Marra E, Passarella S. Cytochrome c is released from mitochondria in a reactive oxygen species (ROS)-dependent fashion and can operate as a ROS scavenger and as a respiratory substrate in cerebellar neurons undergoing excitotoxic death. J. Biol. Chem. 275(47), 37159-37166 (2000). (Pubitemid 32002134)
36. Song IS, Kim HK, Jeong SH et al. Mitochondrial peroxiredoxin III is a potential target for cancer therapy. Int. J. Mol. Sci. 12(10), 7163-7185 (2011).
37. Yu GR, Qin WW, Li JP et al. HIV-TAT-fused FHIT protein functions as a potential pro-apoptotic molecule in hepatocellular carcinoma cells. Biosci. Rep. 32(3), 271-279 (2012).
38. Martin J, St-Pierre MV, Dufour JF. Hit proteins, mitochondria and cancer. Biochim. Biophys. Acta 1807(6), 626-632 (2011).
39. Svilar D, Goellner EM, Almeida KH, Sobol RW. Base excision repair and lesiondependent subpathways for repair of oxidative DNA damage. Antioxid. Redox Signal. 14(12), 2491-2507 (2011).
40. Houston MA, Augenlicht LH, Heerdt BG. Stable differences in intrinsic mitochondrial membrane potential of tumor cell subpopulations reflect phenotypic heterogeneity. Int. J. Cell Biol. 6(9), e25207 (2011). Provides insight into the pathophysiological increase in mitochondrial transmembrane potential in malignant cells.
41. Xue X, You S, Zhang Q et al. Mitaplatin increases sensitivity of tumor cells to cisplatin by inducing mitochondrial dysfunction. Mol. Pharm. 9(3), 634-644 (2012).
42. Fukuda R, Zhang H, Kim JW, Shimoda L, Dang CV, Semenza GL. HIF-1 regulates cytochrome oxidase subunits to optimize efficiency of respiration in hypoxic cells. Cell 129(1), 111-122 (2007). (Pubitemid 46507584)
43. Lecoeur H, Borgne-Sanchez A, Chaloin O et al. HIV-1 Tat protein directly induces mitochondrial membrane permeabilization and inactivates cytochrome c oxidase. Cell Death Dis. 3, E282 (2012).
44. Nonaka M, Hashimoto Y, Takeshima SN, Aida Y. The human immunodeficiency virus type 1 Vpr protein and its carboxy-terminally truncated form induce apoptosis in tumor cells. Cancer Cell Int. 12(9), 20 (2009).
45. Arcangeli A, Crociani O, Lastraioli E, Masi A, Pillozzi S, Becchetti A. Targeting ion channels in cancer: a novel frontier in antineoplastic therapy. Curr. Med. Chem. 16(1), 66-93 (2009).
46. Szabo I, Leanza L, Gulbins E, Zoratti M. Physiology of potassium channels in the inner membrane of mitochondria. Pflugers Arch. 463(2), 231-246 (2012).
47. Cardoso AR, Queliconi BB, Kowaltowski AJ. Mitochondrial ion transport pathways: role in metabolic diseases. Biochim. Biophys. Acta 1797(6-7), 832-838 (2010).
48. Felipe A, Bielanska J, Comes N et al. Targeting the voltage-dependent k (+) channels kv1.3 and kv1.5 as tumor biomarkers for cancer detection and prevention. Curr. Med. Chem. 19(5), 661-674 (2012).
49. Kosztka L, Rusznak Z, Nagy D et al. Inhibition of TASK-3 (KCNK9) channel biosynthesis changes cell morphology and decreases both DNA content and mitochondrial function of melanoma cells maintained in cell culture. Melanoma Res. 21(4), 308-322 (2011).
50. De Stefani D, Raffaello A, Teardo E, Szabo I, Rizzuto R. A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter. Nature 476(7360), 336-340 (2011).
51. Wong R, Steenbergen C, Murphy E. Mitochondrial permeability transition pore and calcium handling. Methods Mol. Biol. 810, 235-242 (2012).
52. Cao X, Zhu H, Ali-Osman F, Lo HW. EGFR and EGFRvIII undergo stress-and EGFR kinase inhibitor-induced mitochondrial translocalization: a potential mechanism of EGFR-driven antagonism of apoptosis. Mol. Cancer 10, 26 (2011).
53. Ren J, Bharti A, Raina D, Chen W, Ahmad R, Kufe D. MUC1 oncoprotein is targeted to mitochondria by heregulin-induced activation of c-Src and the molecular chaperone HSP90. Oncogene 25(1), 20-31 (2006). (Pubitemid 43050000)
54. Sharma SV, Bell DW, Settleman J, Haber DA. Epidermal growth factor receptor mutations in lung cancer. Nat. Rev. Cancer 7(3), 169-181 (2007).
55. Zhu H, Cao X, Ali-Osman F, Keir S, Lo HW. EGFR and EGFRvIII interact with PUMA to inhibit mitochondrial translocalization of PUMA and PUMA-mediated apoptosis independent of EGFR kinase activity. Cancer Lett. 294(1), 101-110 (2010).
56. Cruickshanks N, Hamed H, Bareford MD et al. Lapatinib and obatoclax kill tumor cells through blockade of ERBB1/3/4 and through inhibition of BCL-XL and MCL-1. Mol. Pharmacol. 81(5), 748-758 (2012).
57. Yin L, Kufe D. MUC1-C oncoprotein blocks terminal differentiation of chronic myelogenous leukemia cells by a ROS-mediated mechanism. Genes Cancer 2(1), 56-64 (2011).
58. Yin L, Kosugi M, Kufe D. Inhibition of the MUC1-C oncoprotein induces multiple myeloma cell death by down-regulating TIGAR expression and depleting NADPH. Blood 119(3), 810-816 (2012).
59. Kim TH, Zhao Y, Ding WX et al. Bidcardiolipin interaction at mitochondrial contact site contributes to mitochondrial cristae reorganization and cytochrome C release. Mol. Biol. Cell 15(7), 3061-3072 (2004). (Pubitemid 38850104)
60. Huang CY, Chiang SF, Lin TY, Chiou SH, Chow KC. HIV-1 Vpr triggers mitochondrial destruction by impairing Mfn2-mediated ER-mitochondria interaction. PLoS One 7(3), E33657 (2012). Offers mechanistic insight into HIV-Vpr peptide's multifunctional pro-apoptotic role.
61. Sabbah EN, Druillennec S, Morellet N, Bouaziz S, Kroemer G, Roques BP. Interaction between the HIV-1 protein Vpr and the adenine nucleotide translocator. Chem. Biol. Drug Des. 67(2), 145-154 (2006). (Pubitemid 43881375)
62. Boya P, Pauleau AL, Poncet D, Gonzalez-Polo RA, Zamzami N, Kroemer G. Viral proteins targeting mitochondria: controlling cell death. Biochim. Biophys. Acta 1659(2-3), 178-189 (2004). (Pubitemid 39575505)
63. Ko JK, Choi KH, Peng J et al. Amphipathic tail-anchoring peptide and Bcl-2 homology domain-3 (BH3) peptides from Bcl-2 family proteins induce apoptosis through different mechanisms. J. Biol. Chem. 286(11), 9038-9048 (2011).
64. Papo N, Shai Y. New lytic peptides based on the d.l-amphipathic helix motif preferentially kill tumor cells compared to normal cells. Biochemistry 42(31), 9346-9354 (2003). (Pubitemid 36959242)
65. Madan V, Sanchez-Martinez S, Carrasco L, Nieva JL. A peptide based on the poreforming domain of pro-apoptotic poliovirus 2B viroporin targets mitochondria. Biochim. Biophys. Acta 1798(1), 52-58 (2010).
66. Szewczyk A, Wojtczak L. Mitochondria as a pharmacological target. Pharmacol. Rev. 54(1), 101-127 (2002). (Pubitemid 34211027)
67. Ellerby HM, Arap W, Ellerby LM et al. Anti-cancer activity of targeted pro-apoptotic peptides. Nat. Med. 5(9), 1032-1038 (1999). (Pubitemid 29439574)
68. Fantin VR, Berardi MJ, Babbe H, Michelman MV, Manning CM, Leder P. A bifunctional targeted peptide that blocks HER-2 tyrosine kinase and disables mitochondrial function in HER-2-positive carcinoma cells. Cancer Res. 65(15), 6891-6900 (2005). (Pubitemid 41060728)
69. Smolarczyk R, Cichon T, Graja K, Hucz J, Sochanik A, Szala S. Antitumor effect of RGD-4C-GG-D (KLAKLAK) 2 peptide in mouse B16 (F10) melanoma model. Acta Biochim. Pol. 53(4), 801-805 (2006). (Pubitemid 46090129)
70. Galluzzi L, Kepp O, Trojel-Hansen C, Kroemer G. Non-apoptotic functions of apoptosis-regulatory proteins. EMBO Rep. 13(4), 322-330 (2012).
71. Rudner J, Elsaesser SJ, Muller AC, Belka C, Jendrossek V. Differential effects of anti-apoptotic Bcl-2 family members Mcl-1, Bcl-2, and Bcl-xL on celecoxib-induced apoptosis. Biochem. Pharmacol. 79(1), 10-20 (2010).
72. Schoenwaelder SM, Jackson SP. Bcl-xL-inhibitory BH3 mimetics (ABT-737 or ABT-263) and the modulation of cytosolic calcium flux and platelet function. Blood 119(5), 1320-1321; author reply 1321-1322 (2012).
73. Holinger EP, Chittenden T, Lutz RJ. Bak BH3 peptides antagonize Bcl-xL function and induce apoptosis through cytochrome c-independent activation of caspases. J. Biol. Chem. 274(19), 13298-13304 (1999).
74. Dharap SS, Minko T. Targeted proapoptotic LHRH-BH3 peptide. Pharm. Res. 20(6), 889-896 (2003). (Pubitemid 36628435)
75. Pitter K, Bernal F, Labelle J, Walensky LD. Dissection of the BCL-2 family signaling network with stabilized α-helices of BCL-2 domains. Methods Enzymol. 446, 387-408 (2008). Example of conformationally constrained BH3 peptide mimetics using hydrocarbon stapling.
76. Katz SG, Labelle JL, Godes M, Fisher J, Bird GH, Walensky LD. A stapled BIM BH3 helix restores apoptosis in bim-null mantle cell lymphoma. Presented at: American Society of Hematology Annual Meeting. Atlanta, GA, USA, 4-7 December 2010.
77. Ponassi R, Biasotti B, Tomati V et al. A novel Bim-BH3-derived Bcl-XL inhibitor: biochemical characterization, in vitro, in vivo and ex vivo anti-leukemic activity. Cell Cycle 7(20), 3211-3224 (2008).
78. Gangoda L, Moujalled D, Lee Y, Rahimi A, Puthalakath H. Analysis of the role of Bim as a tumor suppressor in Carney complex syndrome. In: Cell Death in Cancer. De Rode Hoed, Amsterdam, The Netherlands (2012).
79. Rong YP, Bultynck G, Aromolaran AS et al. The BH4 domain of Bcl-2 inhibits ER calcium release and apoptosis by binding the regulatory and coupling domain of the IP3 receptor. Proc. Natl Acad. Sci. USA 106(34), 14397-14402 (2009).
80. Iqbal S, Zhang S, Driss A et al. PDGF upregulates Mcl-1 through activation of b-catenin and HIF-1a-dependent signaling in human prostate cancer cells. PLoS One 7(1), E30764 (2012).
81. Zhong F, Harr MW, Bultynck G et al. Induction of Ca (2) +-driven apoptosis in chronic lymphocytic leukemia cells by peptide-mediated disruption of Bcl-2-IP3 receptor interaction. Blood 117(10), 2924-2934 (2011). Provides insight into the wide cellular homeostatic regulatory and anti-apoptotic role of the Bcl-2 protein.
82. Elgendy M, Sheridan C, Brumatti G, Martin SJ. Oncogenic Ras-induced expression of Noxa and Beclin-1 promotes autophagic celldeath and limits clonogenic survival. Mol. Cell 42(1), 23-35 (2011).
83. Garg AD, Krysko DV, Verfaillie T et al. A novel pathway combining calreticulin exposure and ATP secretion in immunogenic cancer cell death. EMBO J. 31(5), 1062-1079 (2012).
84. Cristofanon S, Fulda S. ABT-737 promotes tBid mitochondrial insertion to enhance TRAIL-induced apoptosis in glioblastoma cells. In: Cell Death in Cancer. De Rode Hoed, Amsterdam, The Netherlands (2012).
85. Glaser SP, Lee EF, Trounson E et al. Anti-apoptotic Mcl-1 is essential for the development and sustained growth of acute myeloid leukemia. Genes Dev. 26(2), 120-125 (2012).
86. Stewart ML, Fire E, Keating AE, Walensky LD. The MCL-1 BH3 helix is an exclusive MCL-1 inhibitor and apoptosis sensitizer. Nat. Chem. Biol. 6(8), 595-601 (2010).
87. Galluzzi L, Kepp O, Tajeddine N, Kroemer G. Disruption of the hexokinase-VDAC complex for tumor therapy. Oncogene 27(34), 4633-4635 (2008).
88. Brenner C, Grimm S. The permeability transition pore complex in cancer cell death. Oncogene 25(34), 4744-4756 (2006). (Pubitemid 44192088)
89. Shoshan-Barmatz V, De Pinto V, Zweckstetter M, Raviv Z, Keinan N, Arbel N. VDAC, a multi-functional mitochondrial protein regulating cell life and death. Mol. Aspects Med. 31(3), 227-285 (2010).
90. Rupprecht R, Papadopoulos V, Rammes G et al. Translocator protein (18 kDa) (TSPO) as a therapeutic target for neurological and psychiatric disorders. Nat. Rev. Drug Discov. 9(12), 971-988 (2010).
91. Taliani S, Pugliesi I, Da Settimo F. Structural requirements to obtain highly potent and selective 18 kDa translocator protein (TSPO) Ligands. Curr. Top Med. Chem. 11(7), 860-886 (2011).
92. Chiara F, Castellaro D, Marin O et al. Hexokinase II detachment from mitochondria triggers apoptosis through the permeability transition pore independent of voltagedependent anion channels. PLoS One 3(3), E1852 (2008).
93. Masgras I, Rasola A, Bernardi P. Induction of the permeability transition pore in cells depleted of mitochondrial DNA. Biochim. Biophys. Acta (2012) (Epub ahead of print).
94. Borgne-Sanchez A, Dupont S, Langonne A et al. Targeted Vpr-derived peptides reach mitochondria to induce apoptosis of aVb3-expressing endothelial cells. Cell Death Differ. 14(3), 422-435 (2007).
95. Park D, Chiu J, Perrone GG, Dilda PJ, Hogg PJ. The tumour metabolism inhibitors GSAO and PENAO react with cysteines 57 and 257 of mitochondrial adenine nucleotide translocase. Cancer Cell Int. 12(1), 11 (2012).
96. Dilda PJ, Decollogne S, Weerakoon L et al. Optimization of the antitumor efficacy of a synthetic mitochondrial toxin by increasing the residence time in the cytosol. J. Med. Chem. 52(20), 6209-6216 (2009).
97. Banerjee J, Ghosh S. Bax increases the pore size of rat brain mitochondrial voltagedependent anion channel in the presence of tBid. Biochem. Biophys. Res. Commun. 323(1), 310-314 (2004). (Pubitemid 39206288)
98. Shoshan-Barmatz V, Ben-Hail D. VDAC, a multi-functional mitochondrial protein as a pharmacological target. Mitochondrion 12(1), 24-34 (2012).
99. Gergalova G, Lykhmus O, Kalashnyk O et al. Mitochondria express a7 nicotinic acetylcholine receptors to regulate Ca accumulation and cytochrome c release: study on isolated mitochondria. PLoS One 7(2), E31361 (2012).
100. Karbowski M, Norris KL, Cleland MM, Jeong SY, Youle RJ. Role of Bax and Bak in mitochondrial morphogenesis. Nature 443(7112), 658-662 (2006). (Pubitemid 44564703)
101. Rosenfeldt MT, Ryan KM. The multiple roles of autophagy in cancer. Carcinogenesis 32(7), 955-963 (2011).
102. White EJ, Martin V, Liu JL et al. Autophagy regulation in cancer development and therapy. Am. J. Cancer Res. 1(3), 362-372 (2011).
103. Hoyer-Hansen M, Jaattela M. Autophagy: an emerging target for cancer therapy. Autophagy 4(5), 574-580 (2008).
104. Gomes LC, Di Benedetto G, Scorrano L. During autophagy mitochondria elongate, are spared from degradation and sustain cell viability. Nat. Cell. Biol. 13(5), 589-598 (2011).
105. Blackstone C, Chang CR. Mitochondria unite to survive. Nat. Cell Biol. 13(5), 521-522 (2011).
106. Zorzano A, Sebastian D, Segales J, Palacin M. The molecular machinery of mitochondrial fusion and fission: an opportunity for drug discovery? Curr. Opin. Drug Discov. Devel. 12(5), 597-606 (2009).
107. Mossalam M, Matissek KJ, Okal A, Constance JE, Lim CS. Direct induction of apoptosis using an optimal mitochondrially targeted p53. Mol. Pharm. 9(5), 1449-1458 (2012).
108. Ferecatu I, Bergeaud M, Rodriguez-Enfedaque A et al. Mitochondrial localization of the low level p53 protein in proliferative cells. Biochem. Biophys. Res. Commun. 387(4), 772-777 (2009).
109. Bergeaud M, Mathieu L, Le Floch N, Mignotte B, Rincheval V, Vayssiere JL. Localization and function of p53 protein at mitochondria in proliferative cells. In: Cell Death in Cancer. De Rode Hoed, Amsterdam, The Netherlands (2012).
110. Von der Malsburg K, Muller JM, Bohnert M et al. Dual role of mitofilin in mitochondrial membrane organization and protein biogenesis. Dev. Cell 21(4), 694-707 (2011).
111. Alirol E, Martinou JC. Mitochondria and cancer: is there a morphological connection? Oncogene 25(34), 4706-4716 (2006). (Pubitemid 44187620)
112. Bouleau S, Parvu-Ferecatu I, Rodriguez-Enfedaque A et al. Fibroblast growth factor 1 inhibits p53-dependent apoptosis in PC12 cells. Apoptosis 12(8), 1377-1387 (2007). (Pubitemid 46988279)
113. Mossalam M, Matissek KJ, Okal A, Constance JE, Lim CS. Direct induction of apoptosis using an optimal mitochondrially targeted p53. Mol. Pharm. 9(5), 1449-1458 (2012).
114. Barnes DJ, Palaiologou D, Panousopoulou E et al. Bcr-Abl expression levels determine the rate of development of resistance to imatinib mesylate in chronic myeloid leukemia. Cancer Res. 65(19), 8912-8919 (2005). (Pubitemid 41377381)
115. Wang JY. Nucleo-cytoplasmic communication in apoptotic response to genotoxic and inflammatory stress. Cell Res. 15(1), 43-48 (2005). (Pubitemid 41653964)
116. Ito Y, Pandey P, Mishra N et al. Targeting of the c-Abl tyrosine kinase to mitochondria in endoplasmic reticulum stress-induced apoptosis. Mol. Cell. Biol. 21(18), 6233-6242 (2001). (Pubitemid 34263523)
117. Lasfer M, Davenne L, Vadrot N et al. Protein kinase PKCd and c-Abl are required for mitochondrial apoptosis induction by genotoxic stress in the absence of p53, p73 and Fas receptor. FEBS Lett. 580(11), 2547-2552 (2006).
118. Constance JE, Despres SD, Nishida A, Lim CS. Selective targeting of c-Abl via a cryptic mitochondrial targeting signal activated by cellular redox status in leukemic and breast cancer cells. Pharm. Res. 29(8), 2317-2328 (2012).
119. Katz C, Zaltsman-Amir Y, Mostizky Y, Kollet N, Gross A, Friedler A. Molecular basis of the interaction between the pro apoptotic tBID protein and mitochondrial carrier homologue 2 (MTCH2): key players in the mitochondrial death pathway. J. Biol. Chem. 287(18), 15016-15023 (2012).
120. Zaltsman Y, Shachnai L, Yivgi-Ohana N et al. MTCH2/MIMP is a major facilitator of tBID recruitment to mitochondria. Nat. Cell. Biol. 12(6), 553-562 (2010).
121. Holley AK, Dhar SK, Xu Y, St Clair DK. Manganese superoxide dismutase: beyond life and death. Amino Acids 42(1), 139-158 (2012).
122. Pedram A, Razandi M, Wallace DC, Levin ER. Functional estrogen receptors in the mitochondria of breast cancer cells. Mol. Biol. Cell 17(5), 2125-2137 (2006). (Pubitemid 44011729)
123. Ennen M, Minig V, Grandemange S et al. Regulation of the high basal expression of the manganese superoxide dismutase gene in aggressive breast cancer cells. Free Radic. Biol. Med. 50(12), 1771-1779 (2011).
124. Zhao Y, Chaiswing L, Velez JM et al. p53 translocation to mitochondria precedes its nuclear translocation and targets mitochondrial oxidative defense protein-manganese superoxide dismutase. Cancer Res. 65(9), 3745-3750 (2005). (Pubitemid 40616352)
125. Altieri DC, Stein GS, Lian JB, Languino LR. TRAP-1, the mitochondrial Hsp90. Biochim. Biophys. Acta 1823(3), 767-773 (2012).
126. Dai C, Whitesell L. HSP90: a rising star on the horizon of anticancer targets. Future Oncol. 1(4), 529-540 (2005).
127. Kamal A, Thao L, Sensintaffar J et al. A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors. Nature 425(6956), 407-410 (2003). (Pubitemid 37187270)
128. Xu H, Shi Y, Wang J et al. A heat shock protein 90 binding domain in endothelial nitric-oxide synthase influences enzyme function. J. Biol. Chem. 282(52), 37567-37574 (2007).
129. Siegelin MD, Dohi T, Raskett CM et al. Exploiting the mitochondrial unfolded protein response for cancer therapy in mice and human cells. J. Clin. Invest. 121(4), 1349-1360 (2011).
130. Kang BH, Tavecchio M, Goel HL et al. Targeted inhibition of mitochondrial Hsp90 suppresses localised and metastatic prostate cancer growth in a genetic mouse model of disease. Br. J. Cancer 104(4), 629-634 (2011).
131. Plescia J, Salz W, Xia F et al. Rational design of shepherdin, a novel anticancer agent. Cancer Cell 7(5), 457-468 (2005). (Pubitemid 40719129)
132. Horibe T, Kawamoto M, Kohno M, Kawakami K. Cytotoxic activity to acute myeloid leukemia cells by Antp-TPR hybrid peptide targeting Hsp90. J. Biosci. Bioeng. (2012).
133. Seigneuric R, Gobbo J, Colas P, Garrido C. Targeting cancer with peptide aptamers. Oncotarget 2(7), 557-561 (2011).
134. Szeto HH, Schiller PW. Novel therapies targeting inner mitochondrial membrane - from discovery to clinical development. Pharm. Res. 28(11), 2669-2679 (2011).
135. Weiss A, Brill B, Borghouts C, Delis N, Mack L, Groner B. Survivin inhibition by an interacting recombinant peptide, derived from the human ferritin heavy chain, impedes tumor cell growth. J. Cancer Res. Clin. Oncol. 138(7), 1205-1220 (2012).
136. Shirakata T, Oka Y, Nishida S et al. WT1 peptide therapy for a patient with chemotherapy-resistant salivary gland cancer. Anticancer Res. 32(3), 1081-1085 (2012).
137. Sinthuvanich C, Veiga AS, Gupta K, Gaspar D, Blumenthal R, Schneider JP. Anticancer ss-hairpin peptides: membrane-induced folding triggers activity. J. Am. Chem. Soc. 134(14), 6210-6217 (2012).
138. Verdine GL. Drugging the undruggable'. Harvey Lect. 102, 1-15 (2006).
139. Borghouts C, Kunz C, Groner B. Current strategies for the development of peptidebased anti-cancer therapeutics. J. Pept. Sci. 11(11), 713-726 (2005). (Pubitemid 41684258)
140. Zhai D, Godoi P, Sergienko E et al. High-throughput fluorescence polarization assay for chemical library screening against anti-apoptotic Bcl-2 family member Bfl-1. J. Biomol. Screen 17(3), 350-360 (2012).
141. Verdine GL, Walensky LD. The challenge of drugging undruggable targets in cancer: lessons learned from targeting BCL-2 family members. Clin. Cancer Res. 13(24), 7264-7270 (2007).
142. Bolhassani A. Potential efficacy of cellpenetrating peptides for nucleic acid and drug delivery in cancer. Biochim. Biophys. Acta 1816(2), 232-246 (2011).
143. Kelley SO, Stewart KM, Mourtada R. Development of novel peptides for mitochondrial drug delivery: amino acids featuring delocalized lipophilic cations. Pharm. Res. 28(11), 2808-2819 (2011).
144. Moreau V, Fleury C, Piquer D et al. PEPOP: computational design of immunogenic peptides. BMC Bioinformatics 9, 71 (2008).
145. Van Walle I, Gansemans Y, Parren PW, Stas P, Lasters I. Immunogenicity screening in protein drug development. Expert Opin. Biol. Ther. 7(3), 405-418 (2007). (Pubitemid 46383483)
146. Chirino AJ, Ary ML, Marshall SA. Minimizing the immunogenicity of protein therapeutics. Drug Discov. Today 9(2), 82-90 (2004). (Pubitemid 38169532)
147. Watt PM. Screening for peptide drugs from the natural repertoire of biodiverse protein folds. Nat. Biotechnol. 24(2), 177-183 (2006). (Pubitemid 43221700)
148. Braun CR, Mintseris J, Gavathiotis E, Bird GH, Gygi SP, Walensky LD. Photoreactive stapled BH3 peptides to dissect the BCL-2 family interactome. Chem. Biol. 17(12), 1325-1333 (2010).
149. Valero JG, Sancey L, Kucharczak J et al. Bax-derived membrane-active peptides act as potent and direct inducers of apoptosis in cancer cells. J. Cell. Sci. 124(Pt 4), 556-564 (2011).
150. Trusheim M, Aitken MC, Berndt ER. Characterizing markets for biopharmaceutical innovations: Do biologics differ from small molecules? (Article 4). Forum Health Econ. Policy 13 (1) 16014 (2010).
151. Kozlowski S, Woodcock J, Midthun K, Sherman RB. Developing the nation's biosimilars program. N. Engl. J. Med. 365(5), 385-388 (2011).
152. Trivigno D, Essmann F, Huber S, Rudner J. The deubiquitinase USP9x controls Mcl-1 levels in response to ionizing radiation. In: Cell Death in Cancer. De Rode Hoed, Amsterdam, The Netherlands (2012).
153. Naumann I, Kappler R, von Schweinitz D, Debatin KM, Fulda S. Bortezomib primes neuroblastoma cells for TRAIL-induced apoptosis by linking the death receptor to the mitochondrial pathway. Clin. Cancer Res. 17(10), 3204-3218 (2011).
154. Certo M, Del Gaizo Moore V, Nishino M et al. Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members. Cancer Cell 9(5), 351-365 (2006). (Pubitemid 43668734)
155. Vrielink J, Heins MS, Setroikromo R et al. Synthetic constrained peptide selectively binds and antagonizes death receptor 5. FEBS J. 277(7), 1653-1665 (2010).
156. Neuzil J, Wang XF, Dong LF, Low P, Ralph SJ. Molecular mechanism of mitocan'-induced apoptosis in cancer cells epitomizes the multiple roles of reactive oxygen species and Bcl-2 family proteins. FEBS Lett. 580(22), 5125-5129 (2006). (Pubitemid 44415781)
157. Chipuk JE, Green DR. Dissecting p53-dependent apoptosis. Cell Death Differ. 13(6), 994-1002 (2006).