Macroautophagy inhibition sensitizes tamoxifen-resistant breast cancer cells and enhances mitochondrial depolarization

Springer Science and Business Media LLC - Tập 112 - Trang 389-403 - 2008
M. A. Qadir1, B. Kwok1, W. H. Dragowska2, K. H. To1, D. Le1, M. B. Bally2, Sharon M. Gorski1
1Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, Canada
2Department of Advanced Therapeutics, British Columbia Cancer Agency, Vancouver, Canada

Tóm tắt

Macroautophagy (autophagy), a process for lysosomal degradation of organelles and long-lived proteins, has been linked to various pathologies including cancer and to the cellular response to anticancer therapies. In the human estrogen receptor positive MCF7 breast adenocarcinoma cell line, treatment with the endocrine therapeutic tamoxifen was shown previously to induce cell cycle arrest, cell death, and autophagy. To investigate specifically the role of autophagy in tamoxifen treated breast cancer cell lines, we used a siRNA approach, targeting three different autophagy genes, Atg5, Beclin-1, and Atg7. We found that knockdown of autophagy, in combination with tamoxifen in MCF7 cells, results in decreased cell viability concomitant with increased mitochondrial-mediated apoptosis. The combination of autophagy knockdown and tamoxifen treatment similarly resulted in reduced cell viability in the breast cancer cell lines, estrogen receptor positive T-47D and tamoxifen-resistant MCF7-HER2. Together, these results indicate that autophagy has a primary pro-survival role following tamoxifen treatment, and suggest that autophagy knockdown may be useful in a combination therapy setting to sensitize breast cancer cells, including tamoxifen-resistant breast cancer cells, to tamoxifen therapy.

Tài liệu tham khảo

WHO. Cited; Available from http://www.who.int/en/ Jordan VC (2003) Tamoxifen: a most unlikely pioneering medicine. Nat Rev Drug Discov 2:205–213 American Cancer Society. Cited; Available from http://www.cancer.org/docroot/home/index.asp Smith CL, Nawaz Z, O’Malley BW (1997) Coactivator and corepressor regulation of the agonist/antagonist activity of the mixed antiestrogen, 4-hydroxytamoxifen. Mol Endocrinol 11:657–666 Caldon CE, Daly RJ, Sutherland RL, Musgrove EA (2006) Cell cycle control in breast cancer cells. J Cell Biochem 97:261–274 Mandlekar S, Kong ANT (2001) Mechanisms of tamoxifen-induced apoptosis. Apoptosis 6:469–477 Ring A, Dowsett M (2004) Mechanisms of tamoxifen resistance. Endocr Relat Cancer 11:643–658 Knuefermann C, Lu Y, Liu B, Jin W, Liang K, Wu L, Schmidt M, Mills GB, Mendelsohn J, Fan Z (2003) HER2/PI-3K/Akt activation leads to a multidrug resistance in human breast adenocarcinoma cells. Oncogene 22:3205–3212 Liang K, Lu Y, Jin W, Ang KK, Milas L, Fan Z (2003) Sensitization of breast cancer cells to radiation by trastuzumab. Mol Cancer Ther 2:1113–1120 Shou J, Massarweh S, Osborne CK, Wakeling AE, Ali S, Weiss H, Schiff R (2004) Mechanisms of tamoxifen resistance: increased estrogen receptor-HER2/neu cross-talk in ER/HER2-positive breast cancer. J Natl Cancer Inst 96:926–935 Bursch W, Ellinger A, Kienzl H, Torok L, Pandey S, Sikorska M, Walker R, Hermann RS (1996) Active cell death induced by the anti-estrogens tamoxifen and ICI 164 384 in human mammary carcinoma cells (MCF-7) in culture: the role of autophagy. Carcinogenesis 17:1595–1607 Bilir A, Altinoz MA, Erkan M, Ozmen V, Aydiner A (2001) Autophagy and nuclear changes in FM3A breast tumor cells after epirubicin, medroxyprogesterone and tamoxifen treatment in vitro. Pathobiology 69:120–126 Shintani T, Klionsky DJ (2004) Autophagy in health and disease: a double-edged sword. Science 306:990–995 Tsukada M, Ohsumi Y (1993) Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. FEBS Lett 333:169–174 Harding TM, Morano KA, Scott SV, Klionsky DJ (1995) Isolation and characterization of yeast mutants in the cytoplasm to vacuole protein targeting pathway. J Cell Biol 131:591–602 Klionsky DJ, Cregg JM, Dunn WA Jr, Emr SD, Sakai Y, Sandoval IV, Sibirny A, Subramani S, Thumm M, Veenhuis M, Ohsumi Y (2003) A unified nomenclature for yeast autophagy-related genes. Dev Cell 5:539–545 Baehrecke EH (2005) Autophagy: dual roles in life and death? Nat Rev Mol Cell Biol, 6:505–510 Levine B, Yuan J (2005) Autophagy in cell death: an innocent convict? J Clin Invest 115:2679–2688 Lum JJ, Bauer DE, Kong M, Harris MH, Li C, Lindsten T, Thompson CB (2005) Growth factor regulation of autophagy and cell survival in the absence of apoptosis. Cell 120:237–248 Hait WN, Jin S, Yang JM (2006) A matter of life or death (or both): understanding autophagy in cancer. Clin Cancer Res 12:1961–1965 Williams A, Jahreiss L, Sarkar S, Saiki S, Menzies FM, Ravikumar B, Rubinsztein DC (2006) Aggregate-prone proteins are cleared from the cytosol by autophagy: therapeutic implications. Curr Top Dev Biol 76:89–101 Djavaheri-Mergny M, Amelotti M, Mathieu J, Besancon F, Bauvy C, Souquere S, Pierron G, Codogno P (2006) NF-kappaB activation represses tumor necrosis factor-alpha-induced autophagy. J Biol Chem 281:30373–30382 Nakai A, Yamaguchi O, Takeda T, Higuchi Y, Hikoso S, Taniike M, Omiya S, Mizote I, Matsumura Y, Asahi M, Nishida K, Hori M, Mizushima N, Otsu K (2007) The role of autophagy in cardiomyocytes in the basal state and in response to hemodynamic stress. Nat Med 13:619–624 Yu L, Alva A, Su H, Dutt P, Freundt E, Welsh S, Baehrecke EH, Lenardo MJ (2004) Regulation of an ATG7-beclin 1 program of autophagic cell death by caspase-8. Science 304:1500–1502 Shimizu S, Kanaseki T, Mizushima N, Mizuta T, Arakawa-Kobayashi S, Thompson CB, Tsujimoto Y (2004) Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes. Nat Cell Biol 6:1221–1228 Kondo Y, Kanzawa T, Sawaya R, Kondo S (2005) The role of autophagy in cancer development and response to therapy. Nat Rev Cancer 5:726–734 Kondo Y, Kondo S (2006) Autophagy and cancer therapy. Autophagy 2:85–90 Bauvy C, Gane P, Arico S, Codogno P, Ogier-Denis E (2001) Autophagy delays sulindac sulfide-induced apoptosis in the human. Exp Cell Res 268:139–149 Kanzawa T, Zhang L, Xiao L, Germano IM, Kondo Y, Kondo S (2005) Arsenic trioxide induces autophagic cell death in malignant glioma cells by upregulation of mitochondrial cell death protein BNIP3. Oncogene 24:980–991 Paglin S, Hollister T, Delohery T, Hackett N, McMahill M, Sphicas E, Domingo D, Yahalom J (2001) A novel response of cancer cells to radiation involves autophagy and formation of acidic vesicles. Cancer Res 61:439–444 Ito H, Daido S, Kanzawa T, Kondo S, Kondo Y (2005) Radiation-induced autophagy is associated with LC3 and its inhibition sensitizes malignant glioma cells. Int J Oncol 26:1401–1410 Klionsky DJ, Cuervo AM, Seglen PO (2007) Methods for monitoring autophagy from yeast to human. Autophagy 3:181–206 Abedin MJ, Wang D, McDonnell MA, Lehmann U, Kelekar A (2007) Autophagy delays apoptotic death in breast cancer cells following DNA damage. Cell Death Differ 14:500–510 Katayama M, Kawaguchi T, Berger MS, Pieper RO (2006) DNA damaging agent-induced autophagy produces a cytoprotective adenosine triphosphate surge in malignant glioma cells. Cell Death Differ 14:548–558 Amaravadi RK, Yu D, Lum JJ, Bui T, Christophorou MA, Evan GI, Thomas-Tikhonenko A, Thompson CB (2007) Autophagy inhibition enhances therapy-induced apoptosis in a Myc-induced model of lymphoma. J Clin Invest 117:326–336 Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T, Kominami E, Ohsumi Y, Yoshimori T (2000) LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J 19:5720–5728 Niemann A, Takatsuki A, Elsasser HP (2000) The lysosomotropic agent monodansylcadaverine also acts as a solvent polarity probe. J Histochem Cytochem 48:251–258 Niemann A, Baltes J, Elsasser HP (2001) Fluorescence properties and staining behavior of monodansylpentane, a structural homologue of the lysosomotropic agent monodansylcadaverine. J Histochem Cytochem 49:177–185 Munafo DB, Colombo MI (2001) A novel assay to study autophagy: regulation of autophagosome vacuole size by amino acid deprivation. J Cell Sci 114:3619–3629 Mizushima N (2004) Methods for monitoring autophagy. Int J Biochem Cell Biol 36:2491–2502 Luo S, Rubinsztein DC (2007) Atg5 and Bcl-2 provide novel insights into the interplay between apoptosis and autophagy. Cell Death Differ 14:1247–1250 Yousefi S, Perozzo R, Schmid I, Ziemiecki A, Schaffner T, Scapozza L, Brunner T, Simon HU (2006) Calpain-mediated cleavage of Atg5 switches autophagy to apoptosis. Nat Cell Biol 8:1124–1132 Lockshin RA, Zakeri Z (2004) Apoptosis, autophagy, and more. Int J Biochem Cell Biol 36:2405–2419 Melino G, Knight RA, Nicotera P (2005) How many ways to die? How many different models of cell death? Cell Death Differ 12(Suppl 2):1457–1462 Bachmann-Moisson N, Barberi-Heyob M, Merlin JL, Ledrich ML, Batt AM, Guillemin F (1996) [Cytotoxicity of tamoxifen and its principal metabolites in human breast cancer cell lines]. Bull Cancer 83:808–815 Jiang X, Roth L, Lai C, Li X (2006) Profiling activities of transcription factors in breast cancer cell lines. Assay Drug Dev Technol 4:293–305 Benz CC, Scott GK, Sarup JC, Johnson RM, Tripathy D, Coronado E, Shepard HM, Osborne CK (1992) Estrogen-dependent, tamoxifen-resistant tumorigenic growth of MCF-7 cells transfected with HER2/neu. Breast Cancer Res Treat 24:85–95 Hoyer-Hansen M, Bastholm L, Mathiasen IS, Elling F, Jaattela M (2005) Vitamin D analog EB1089 triggers dramatic lysosomal changes and beclin 1-mediated autophagic cell death. Cell Death Differ 12(10):1297–1309 Bao Q, Shi Y (2007) Apoptosome: a platform for the activation of initiator caspases. Cell Death Differ 14:56–65 Boya P, Gonzalez-Polo RA, Casares N, Perfettini JL, Dessen P, Larochette N, Metivier D, Meley D, Souquere S, Yoshimori T, Pierron G, Codogno P, Kroemer G (2005) Inhibition of macroautophagy triggers apoptosis. Mol Cell Biol 25:1025–1040 Gonzalez-Polo RA, Boya P, Pauleau AL, Jalil A, Larochette N, Souquere S, Eskelinen EL, Pierron G, Saftig P, Kroemer G (2005) The apoptosis/autophagy paradox: autophagic vacuolization before apoptotic death. J Cell Sci 118:3091–3102 Liang XH, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H, Levine B (1999) Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 402:672–676 Janicke RU, Sprengart ML, Wati MR, Porter AG (1998) Caspase-3 is required for DNA fragmentation and morphological changes associated with apoptosis. J Biol Chem 273:9357–9360 Arpino G, Weiss H, Lee AV, Schiff R, De Placido S, Osborne CK, Elledge RM (2005) Estrogen receptor-positive, progesterone receptor-negative breast cancer: association with growth factor receptor expression and tamoxifen resistance. J Natl Cancer Inst 97:1254–1261 Borg A, Baldetorp B, Ferno M, Killander D, Olsson H, Ryden S, Sigurdsson H (1994) ERBB2 amplification is associated with tamoxifen resistance in steroid-receptor positive breast cancer. Cancer Lett 81:137–144 Argiris A, Wang CX, Whalen SG, DiGiovanna MP (2004) Synergistic interactions between tamoxifen and trastuzumab (herceptin). Clin Cancer Res 10:1409–1420 Guarneri V, Conte PF (2004) The curability of breast cancer and the treatment of advanced disease. Eur J Nucl Med Mol Imaging 31(Suppl 1):S149–S161 Johnston SR (2005) Combinations of endocrine and biological agents: present status of therapeutic and presurgical investigations. Clin Cancer Res 11:889s–899s Menard S, Casalini P, Campiglio M, Pupa SM, Tagliabue E (2004) Role of HER2/neu in tumor progression and therapy. Cell Mol Life Sci 61:2965–2978