Pioglitazone, a PPAR-gamma ligand, exerts cytostatic-cytotoxic effects against cancer cells, that do not result from inhibition of proteasome

• Autorzy: Mrowka P. , Glodkowska E. , Mlynarczuk-Bialy I. , Bialy L. , Kuckelkorn U. , Nowis D. , Makowski M. , Legat M. , Golab J.
• Języki publikacji: EN

Abstrakty

EN

Thiazolidinediones are oral antidiabetic agents that activate peroxisome proliferator-activated receptor-gamma (PPAR-γ) and exert potent antioxidant and anti-inflammatory properties. It has also been shown that PPAR-γ agonists induce G0/G1 arrest and apoptosis of malignant cells. Some of these effects have been suggested to result from inhibition of proteasome activity in target cells. The aim of our studies was to critically evaluate the cytostatic/cytotoxic effects of one of thiazolidinediones (pioglitazone) and its influence on proteasome activity. Pioglitazone exerted dose-dependent cytostatic/cytotoxic effects in MIA PaCa-2 cells. Incubation of tumor cells with pioglitazone resulted in increased levels of p53 and p27 and decreased levels of cyclin D1. Accumulation of polyubiquitinated proteins within cells incubated with pioglitazone suggested dysfunction of proteasome activity. However, we did not observe any influence of pioglitazone on the activity of isolated proteasome and on the proteolytic activity in lysates of pioglitazone-treated MIA PaCa-2 cells. Further, treatment with pioglitazone did not cause an accumulation of fluorescent proteasome substrates in transfected HeLa cells expressing unstable GFP variants. Our results indicate that pioglitazone does not act as a direct or indirect proteasome inhibitor.

Słowa kluczowe

EN

cytostatic effect; proteasome; cancer cell; antidiabetic drug; cytotoxic effect; thiazolidinedione; plioglitazone; peroxisome proliferator-activated receptor-gamma

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 2008
• Tom: 55
• Numer: 1
• Opis fizyczny: p.75-84,fig.,ref.

Twórcy

autor

Mrowka P.

• The Medical University of Warsaw, Chalubinskiego 5, 02-004 Warsaw, Poland

autor

Glodkowska E.

autor

Mlynarczuk-Bialy I.

autor

Bialy L.

autor

Kuckelkorn U.

autor

Nowis D.

autor

Makowski M.

autor

Legat M.

autor

Golab J.

Bibliografia

• Akasaki Y, Liu G, Matundan HH, Ng H, Yuan X, Zeng Z, Black KL, Yu JS (2006) A peroxisome proliferator-activated receptor-gamma agonist, troglitazone, facilitates caspase-8 and -9 activities by increasing the enzymatic activity of protein-tyrosine phosphatase-lB on human glioma cells. J Biol Chem 281: 6165-6174.
• Brockman JA, Gupta RA, Dubois RN (1998) Activation of PPAR gamma leads to inhibition of anchorage-independent growth of human colorectal cancer cells. Gastroenterology 115: 1049-1055.
• Caraglia M, Marra M, Mancinelli F, D'Ambrosio G, Massa R, Giordano A, Budillon A, Abbruzzese A, Bismuto E (2005) Electromagnetic fields at mobile phone frequency induce apoptosis and inactivation of the multi-chaperone complex in human epidermoid cancer cells. J Cell Physiol 204: 539-548.
• Cecchi M, Caccese E, Messori A (2005) Bortezomib in multiple myeloma. N Engl J Med 353: 1297-1298; author reply 1297-1298.
• Cellai I, Benvenuti S, Luciani P, Galli A, Ceni E, Simi L, Baglioni S, Muratori M, Ottanelli B, Serio M, Thiele CJ, Peri A (2006) Antineoplastic effects of rosiglitazone and PPAR gamma transactivation in neuroblastoma cells. Br J Cancer 95: 879-888.
• Chang TH, Szabo E (2000) Induction of differentiation and apoptosis by ligands of peroxisome proliferator-activated receptor gamma in non-small cell lung cancer. Cancer Res 60: 1129-1138.
• Chattopadhyay N, Singh DP, Heese O, Godbole MM, Sinohara T, Black PM, Brown EM (2000) Expression of peroxisome proliferator-activated receptors (PPARS) in human astrocytic cells: PPAR gamma agonists as inducers of apoptosis. J Neurosci Res 61: 67-74.
• Chen F, Harrison LE (2005) Ciglitazone-induced cellular anti-proliferation increases p27kipl protein levels through both increased transcriptional activity and inhibition of proteasome degradation. Cell Signal 17: 809-816.
• Coux O, Tanaka K, Goldberg AL (1996) Structure and functions of the 20S and 26S proteasomes. Annu Rev Biochem 65: 801-847.
• Davies GF, Roesler WJ, Ovsenek N, Bharadwaj LA (2003) Troglitazone reduces heat shock protein 70 content in primary rat hepatocytes by a ubiquitin proteasome independent mechanism. Pharmacol Res 48: 119-126.
• Desvergne B, Wahli W (1999) Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr Rev 20: 649-688.
• Dragnev KH, Freemantie SJ, Spinella MJ, Dmitrovsky E (2001) Cyclin proteolysis as a retinoid cancer prevention mechanism. Ann NY Acad Sci USA 952: 13-22.
• Drakos E, Thomaides A, Medeiros LJ, Li J, Leventaki V, Konopleva M, Andreeff M, Rassidakis GZ (2007) Inhibition of p53-murine double minute 2 interaction by nutlin-3A stabilizes p53 and induces cell cycle arrest and apoptosis in Hodgkin lymphoma. Clin Cancer Res 13: 3380-3387.
• Eibl G, Wente MN, Reber HA, Hines OJ (2001) Peroxisome proliferator-activated receptor gamma induces pancreatic cancer cell apoptosis. Biochem Biophys Res Commun 287: 522-529.
• Elnemr A, Ohta T, Iwata K, Ninomia I, Fushida S, Nishimura G, Kitagawa H, Kayahara M, Yamamoto M, Terada T, Miwa K (2000) PPAR gamma ligand (thiazolidinedione) induces growth arrest and differentiation markers of human pancreatic cancer cells. Int J Oncol 17: 1157-1164.
• Elstner E, Muller C, Koshizuka K, Williamson EA, Park D, Asou H, Shintaku P, Said JW, Heber D, Koeffler HP (1998) Ligands for peroxisome proliferator-activated receptor gamma and retinoic acid receptor inhibit growth and induce apoptosis of human breast cancer cells in vitro and in BNX mice. Proc Natl Acad Sci USA 95: 8806-8811.
• Emery MN, Leontiou C, Bonner SE, Merulli C, Nanzer AM, Musat M, Galloway M, Powell M, Nikookam K, Korbonits M, Grossman AB (2006) PPAR-gamma expression in pituitary tumours and the functional activity of the glitazones: evidence that any anti-proliferative effect of the glitazones is independent of the PPAR- gamma receptor. Clin Endocrinol (Oxf) 65: 389-395.
• Fan XM, Wong BC, Wang WP, Zhou XM, Cho CH, Yuen ST, Leung SY, Lin MC, Kung HF, Lam SK (2001) Inhibition of proteasome function induced apoptosis in gastric cancer. Int J Cancer 93: 481-488.
• Feng Q, Sekula D, Muller R, Freemantle SJ, Dmitrovsky E (2007) Uncovering residues that regulate cyclin D1 pro- teasomal degradation. Oncogene 26: 5098-5106.
• Gillies PS, Dunn CJ (2000) Pioglitazone. Drugs 60: 333-343; discussion 344-345.
• Grune T (2000) Oxidative stress, aging and the proteasomal system. Biogerontology 1: 31-40.
• Han S, Roman J (2006) Rosiglitazone suppresses human lung carcinoma cell growth through PPAR gamma-dependent and PPAR gamma-independent signal pathways. Mol Cancer Ther 5: 430-437.
• Hazra S, Batra RK, Tai HH, Sharma S, Cui X, Dubinett SM (2007) Pioglitazone and rosiglitazone decrease prostaglandin E2 in non-small-cell lung cancer cells by up-regulating 15-hydroxyprostaglandin dehydrogenase. Mol Pharmacol 71: 1715-1720.
• Hermann J, Gulati R, Napoli C, Woodrum JE, Lerman LO, Rodriguez-Porcel M, Sica V, Simari RD, Ciechanover A, Lerman A (2003) Oxidative stress-related increase in ubiquitination in early coronary atherogenesis. FASEB J 17: 1730-1732.
• Huang JW, Shiau CW, Yang YT, Kulp SK, Chen KF, Brueggemeier RW, Shapiro CL, Chen CS (2005) Peroxisome proliferator-activated receptor gamma-independent ablation of cyclin D1 by thiazolidinediones and their derivatives in breast cancer cells. Mol Pharmacol 67: 1342-1348.
• Kahn CR, Chen L, Cohen SE (2000) Unraveling the mechanism of action of thiazolidinediones. J Clin Invest 106: 1305-1307.
• Kloetzel PM (2001) Antigen processing by the proteasome. Nat Rev Mol Cell Biol 2: 179-187.
• Kloetzel PM (2004) Generation of major histocompatibility complex class I antigens: functional interplay between proteasomes and TPPII. Nat Immunol 5: 661-669.
• Kloetzel PM (2004) The proteasome and MHC class I antigen processing. Biochim Biophys Acta 1695: 225-233.
• Kudo Y, Takata T, Ogawa I, Kaneda T, Sato S, Takekoshi T, Zhao M, Miyauchi M, Nikai H (2000) p27Kipl accumulation by inhibition of proteasome function induces apoptosis in oral squamous cell carcinoma cells. Clin Cancer Res 6: 916-923.
• Lecka-Czernik B, Moerman EJ, Grant DF, Lehmann JM, Manolagas SC, Jilka RL (2002) Divergent effects of selective peroxisome proliferator-activated receptor-gamma 2 ligands on adipocyte versus osteoblast differentiation. Endocrinology 143: 2376-2384.
• Lee CJ, Han JS, Seo CY, Park TH, Kwon HC, Jeong JS, Kim IH, Yun J, Bae YS, Kwak JY, Park JI (2006) Pioglitazone, a synthetic ligand for PPAR gamma, induces apoptosis in RB-deficient human colorectal cancer cells. Apoptosis 11: 401-411.
• Leung WK, Bai AH, Chan VY, Yu J, Chan MW, To KF, Wu JR, Chan KK, Fu YG, Chan FK, Sung JJ (2004) Effect of peroxisome proliferator activated receptor gamma ligands on growth and gene expression profiles of gastric cancer cells. Gut 53: 331-338.
• Liu Y, Meng Y, Liu H, Li J, Fu J, Chen X (2006) Growth inhibition and differentiation induced by peroxisome proliferator activated receptor gamma ligand rosiglitazone in human melanoma cell line a375. Med Oncol 23: 393-402.
• Ludwig H, Khayat D, Giaccone G, Facon T (2005) Proteasome inhibition and its clinical prospects in the treatment of hematologic and solid malignancies. Cancer 104: 1794-1807.
• Mani A, Gelmann EP (2005) The ubiquitin-proteasome pathway and its role in cancer. J Clin Oncol 23: 4776- 4789.
• Meiners S, Ludwig A, Stangl V, Stangl K (2007) Proteasome inhibitors: Poisons and remedies. Med Res Rev 28: 309-327.
• Michalik L, Desvergne B, Dreyer C, Gavillet M, Laurini RN, Wahli W (2002) PPAR expression and function during vertebrate development, Int J Dev Biol 46: 105- 114.
• Morosetti R, Servidei T, Mirabella M, Rutella S, Mangiola A, Maira G, Mastrangelo R, Koeffler HP (2004) The PPAR gamma ligands PGJ2 and rosiglitazone show a differential ability to inhibit proliferation and to induce apoptosis and differentiation of human glioblastoma cell lines, Int J Oncol 25: 493-502.
• Motomura W, Takahashi N, Nagamine M, Sawamukai M, Tanno S, Kohgo Y, Okumura T (2004) Growth arrest by troglitazone is mediated by p27Kipl accumulation, which results from dual inhibition of proteasome activity and Skp2 expression in human hepatocellular carcinoma cells. Int J Cancer 108: 41-46.
• Nam DH, Ramachandran S, Song DK, Kwon KY, Jeon DS, Shin SJ, Kwon SH, Cha SD, Bae I, Cho CH (2007) Growth inhibition and apoptosis induced in human leiomyoma cells by treatment with the PPAR gamma ligand ciglitizone. Mol Hum Reprod 13: 829-836.
• Nomura S, Nakajima A, Ishimine S, Matsuhashi N, Kadowaki T, Kaminishi M (2006) Differential expression of peroxisome proliferator-activated receptor in histologically different human gastric cancer tissues. J Exp Clin Cancer Res 25: 443-448.
• Nowis D, Legat M, Grzela T, Niderla J, Wilczek E, Wilczynski GM, Glodkowska E, Mrowka P, Issat T, Dulak J, Jozkowicz A, Was H, Adamek M, Wrzosek A, Nazarewski S, Makowski M, Stoklosa T, Jakobisiak M, Golab J (2006) Heme oxygenase-1 protects tumor cells against photodynamic therapy-mediated cytotoxicity. Oncogene 25: 3365-3374.
• Occhi G, Albiger N, Berlucchi S, Gardiman M, Scanarini M, Scienza R, Fassina A, Mantero F, Scaroni C (2007) Peroxisome proliferator-activated receptor gamma in the human pituitary gland: expression and splicing pattern in adenomas versus normal pituitary. J Neuroendocrinol 19: 552-559.
• Park JW, Zarnegar R, Kanauchi H, Wong MG, Hyun WC, Ginzinger DG, Lobo M, Cotter P, Duh QY, Clark OH (2005) Troglitazone, the peroxisome proliferator-activated receptor-gamma agonist, induces antiproliferation and redifferentiation in human thyroid cancer cell lines. Thyroid 15: 222-231.
• Peters JM, Cejka Z, Harris JR, Kleinschmidt JA, Baumeister W (1993) Structural features of the 26 S proteasome complex. J Mol Biol 234: 932-937.
• Pigneux A, Mahon FX, Moreau-Gaudry F, Uhalde M, Verneuil HD, Lacombe F, Reiffers J, Milpied N, Praloran V, Belloc F (2007) Proteasome inhibition specifically sensitizes leukemic cells to anthracyclin-induced apoptosis through the accumulation of Bim and Bax pro-apoptotic proteins. Cancer Biol Ther 6: 603-611.
• Qin C, Burghardt R, Smith R, Wormke M, Stewart J, Safe S (2003) Peroxisome proliferator-activated receptor gamma agonists induce proteasome-dependent degradation of cyclin D1 and estrogen receptor alpha in MCF-7 breast cancer cells. Cancer Res 63: 958-964.
• Radhakrishnan SK, Gartel AL (2005) The PPAR-gamma agonist pioglitazone post-transcriptionally induces p21 in PC3 prostate cancer but not in other cell lines. Cell Cycle 4: 582-584.
• Ray DM, Akbiyik F, Phipps RP (2006) The peroxisome proliferator-activated receptor gamma (PPAR gamma) ligands 15-deoxy-Deltal2,14-prostaglandin J2 and ciglitazone induce human B lymphocyte and B cell lymphoma apoptosis by PPAR gamma-independent mechanisms. J Immunol 177: 5068-5076.
• Ray DM, Bernstein SH, Phipps RP (2004) Human multiple myeloma cells express peroxisome proliferator-ac- tivated receptor gamma and undergo apoptosis upon exposure to PPAR gamma ligands. Clin Immunol 113: 203-213.
• Richardson PG, Anderson KC (2003) Bortezomib: a novel therapy approved for multiple myeloma. Clin Adv Hematol Oncol 1: 596-600.
• Rumi MA, Ishihara S, Kadowaki Y, Ortega-Cava CF, Kazumori H, Kawashima K, Yoshino N, Yuki T, Ishimura N, Kinoshita Y (2004) Peroxisome proliferator-activated receptor gamma-dependent and -independent growth inhibition of gastrointestinal tumour cells. Genes Cells 9: 1113-1123.
• Sarraf P, Mueller E, Jones D, King FJ, DeAngelo DJ, Partridge JB, Holden SA, Chen LB, Singer S, Fletcher C, Spiegelman BM (1998) Differentiation and reversal of malignant changes in colon cancer through PPAR gamma. Nat Med 4: 1046-1052.
• Saville MK, Sparks A, Xirodimas DP, Wardrop J, Stevenson LF, Bourdon JC, Woods YL, Lane DP (2004) Regulation of p53 by the ubiquitin-conjugating enzymes UbcH5B/C in vivo. J Biol Chem 279: 42169-42181.
• Scudiero DA, Shoemaker RH, Paull KD, Monks A, Tierney S, Nofziger TH, Currens MJ, Seniff D, Boyd MR (1988) Evaluation of a soluble tetrazolium/formazan assay for cell growth and drug sensitivity in culture using human and other tumor cell lines. Cancer Res 48: 4827-4833.
• Shen Y, Ballar P, Apostolou A, Doong H, Fang S (2007) ER stress differentially regulates the stabilities of ERAD ubiquitin ligases and their substrates. Biochem Biophys Res Commun 352: 919-924.
• Shiau CW, Yang CC, Kulp SK, Chen KF, Chen CS, Huang J W (2005) Thiazolidenediones mediate apoptosis in prostate cancer cells in part through inhibition of Bcl- xL/Bcl-2 functions independently of PPAR gamma. Cancer Res 65: 1561-1569.
• Spataro V, Norbury C, Harris AL (1998) The ubiquitin-pro teasome pathway in cancer. Br J Cancer 77: 448-455.
• Strakova N, Ehrmann J, Dzubak P, Bouchal J, Kolar Z The synthetic ligand of peroxisome proliferator-activated receptor-gamma ciglitazone affects human glioblastoma cell lines. J Pharmacol Exp Ther 309: 1239-1247.
• Subbarayan V, Sabichi AL, Kim J, Llansa N, Logothetis CJ, Lippman SM, Menter DG (2004) Differential peroxisome proliferator-activated receptor-gamma isoform expression and agonist effects in normal and malignant prostate cells. Cancer Epidemiol Biomarkers Prev 13: 1710-1716.
• Suh N, Wang Y, Williams CR, Risingsong R, Gilmer T, Willson TM, Sporn MB (1999) A new ligand for the peroxisome proliferator-activated receptor-gamma (PPAR-gamma), GW7845, inhibits rat mammary carcinogenesis. Cancer Res 59: 5671-5673.
• Takahashi N, Okumura T, Motomura W, Fujimoto Y, Kawabata I, Kohgo Y (1999) Activation of PPAR gamma inhibits cell growth and induces apoptosis in human gastric cancer cells. FEBS Lett 455: 135-139.
• Theocharis S, Margeli A, Vielh P, Kouraklis G (2004) Peroxisome proliferator-activated receptor-gamma ligands as cell-cycle modulators. Cancer Treat Rev 30: 545-554.
• Vignati S, Albertini V, Rinaldi A, Kwee I, Riva C, Oldrini R, Capella C, Bertoni F, Carbone GM, Catapano CV (2006) Cellular and molecular consequences of peroxisome proliferator-activated receptor-gamma activation in ovarian cancer cells. Neoplasia 8: 851-861.
• Wang T, Xu J, Yu X, Yang R, Han ZC (2006) Peroxisome proliferator-activated receptor gamma in malignant diseases. Crit Rev Oncol Hematol 58: 1-14.
• Weber SM, Chambers KT, Bensch KG, Scarim AL, Corbett JA (2004) PPAR gamma ligands induce ER stress in pancreatic beta-cells: ER stress activation results in attenuation of cytokine signaling. Am J Physiol Endocrinol Metab 287: E1171-E1177.
• Wlodawer A (1995) Proteasome: a complex protease with a new fold and a distinct mechanism. Structure 3: 417- 420.
• Yan XB, Yang DS, Gao X, Feng J, Shi ZL, Ye Z (2007) Caspase-8 dependent osteosarcoma cell apoptosis induced by proteasome inhibitor MG132. Cell Biol Int 31: 1136- 1143.
• Yang CC, Wang YC, Wei S, Lin LF, Chen CS, Lee CC, Lin CC (2007) Peroxisome proliferator-activated receptor gamma-independent suppression of androgen receptor expression by troglitazone mechanism and pharmacologic exploitation. Cancer Res 67: 3229-3238.
• Yang YC, Tsao YP, Ho TC, Choung IP (2007) Peroxisome proliferator-activated receptor-gamma agonists cause growth arrest and apoptosis in human ovarian carcinoma cell lines. Int J Gynecol Cancer 17: 418-425.
• Yin F, Bruemmer D, Blaschke F, Hsueh WA, Law RE, Herle AJ (2004) Signaling pathways involved in induction of GADD45 gene expression and apoptosis by troglitazone in human MCF-7 breast carcinoma cells. Oncogene 23: 4614-1623.
• Yu J, Tiwari S, Steiner P, Zhang L (2003) Differential apoptotic response to the proteasome inhibitor Bortezomib [VELCADE, PS-341] in Bax-deficient and p21-deficient colon cancer cells. Cancer Biol Ther 2: 694-699.
• Zavrski I, Jakob C, Kaiser M, Fleissner C, Heider U, Sezer O (2007) Molecular and clinical aspects of proteasome inhibition in the treatment of cancer. Recent Results Cancer Res 176: 165-176.
• Zhang WG, Yu JP, Wu QM, Tong Q, Li SB, Wang XH, Xie GJ (2004) Inhibitory effect of ubiquitin-proteasome pathway on proliferation of esophageal carcinoma cells. World J Gastroenterol 10: 2779-2784.
• Zhu Q, Wani G, Yao J, Patnaik S, Wang QE, El-Mahdy MA, Praetorius-Ibba M, Wani AA (2007) The ubiquitin- proteasome system regulates p53-mediated transcription at p21wafl promoter. Oncogene 26: 4199-4208.