Top

Published in:

01-08-2011 | PRECLINICAL STUDIES

Effects of the microtubule stabilizing agent peloruside A on the proteome of HL-60 cells

Authors: Anja Wilmes, Pisana Rawson, Lifeng Peng, Danyl McLauchlan, Peter T. Northcote, T. William Jordan, John H. Miller

Published in: Investigational New Drugs | Issue 4/2011

Summary

Peloruside A, isolated from the marine sponge Mycale hentscheli, has a similar mechanism of action to paclitaxel (Taxol®), a drug used clinically to treat tumors of the breast, ovary and lung. Paclitaxel and peloruside stabilize the polymerized form of tubulin and arrest cells in G₂/M of the cell cycle. We have therefore used two-dimensional electrophoresis of proteins to examine the effect of peloruside A on the human HL-60 promyeloid leukemic cell line. Our goals included investigation whether affected proteins could be mapped onto pathways that predicted the cellular effects of this compound. In response to 100 nM peloruside A treatment for 24 h, seventeen identified proteins showed significant change in abundance with fourteen increases and three decreases. Use of Ingenuity Pathways Analysis confirmed that peloruside A affected pathways consistent with the known effects on microtubules and apoptosis. Our results also indicate a potential role of c-Myc in the cellular actions of peloruside consistent with an induction of aneuploidy seen at low concentrations of peloruside.

Available only for authorised users

West LM, Northcote PT, Battershill CN (2000) Peloruside A: a potent cytotoxic macrolide isolated from the New Zealand marine sponge Mycale sp. J Org Chem 65:445–449PubMedCrossRef

Hood KA, Bäckström BT, West LM, Northcote PT, Berridge MV, Miller JH (2001) The novel cytotoxic sponge metabolite peloruside A, structurally similar to bryostatin-1, has unique bioactivity independent of protein kinase C. Anticancer Drug Des 16:155–166PubMed

Miller JH, Rouwé B, Gaitanos TN, Hood KA, Crume KP, Bäckström BT, La Flamme AC, Berridge MV, Northcote PT (2004) Peloruside A enhances apoptosis in H-ras-transformed cells and is cytotoxic to proliferating T cells. Apoptosis 9:785–796PubMedCrossRef

Hood KA, West LM, Rouwé B, Northcote PT, Berridge MV, Wakefield SJ, Miller JH (2002) Peloruside A, a novel antimitotic agent with paclitaxel-like microtubule-stabilizing activity. Cancer Res 62:3356–3360PubMed

Schiff PB, Fant J, Horwitz SB (1979) Promotion of microtubule assembly in vitro by taxol. Nature 277:665–667PubMedCrossRef

Spratlin J, Sawyer MB (2007) Pharmacogenetics of paclitaxel metabolism. Crit Rev Oncol Hematol 61:222–229PubMedCrossRef

Rowinsky EK, Eisenhauer EA, Chaudhry V, Arbuck SG, Donehower RC (1993) Clinical toxicities encountered with paclitaxel (Taxol). Semin Oncol 20:1–15PubMed

Horwitz SB, Cohen D, Rao S, Ringel I, Shen HJ, Yang CP (1993) Taxol: mechanism of action and resistance. J Natl Cancer Inst Monogr 55:15–61

Gaitanos TN, Buey RM, Díaz JF, Northcote PT, Teesdale-Spittle P, Andreu JM, Miller JH (2004) Peloruside A does not bind to the taxoid site on beta-tubulin and retains its activity in multi-drug-resistant cell lines. Cancer Res 64:5063–5067PubMedCrossRef

10.

Huzil JT, Chik JK, Slysz GW, Freedman H, Tuszynski J, Taylor RE, Sackett DL, Schriemer DC (2008) A unique mode of microtubule stabilization induced by peloruside A. J Mol Biol 378:1016–1030PubMedCrossRef

11.

Tonge R, Shaw J, Middleton B, Rowlinson R, Rayner S, Young J, Prognan F, Hawkins E, Currie I, Davison M (2001) Validation and development of fluorescence two-dimensional differential gel electrophoresis proteomics technology. Proteomics 1:377–396PubMedCrossRef

12.

Lee KH, Yim EK, Kim CJ, Namkoong SE, Um SJ, Park JS (2005) Proteomic analysis of anti-cancer effects by paclitaxel treatment in cervical cancer cells. Gynecol Oncol 98:45–53PubMedCrossRef

13.

MacKeigan JP, Clements CM, Lich JD, Pope RM, Hod Y, Ting JP (2003) Proteomic profiling drug-induced apoptosis in non-small cell lung carcinoma: identification of RS/DJ-1 and RhoGDIalpha. Cancer Res 63:6928–6934PubMed

14.

Dowling P, Meleady P, Dowd A, Henry M, Glynn S, Clynes M (2007) Proteomic analysis of isolated membrane fractions from superinvasive cells. Biochim Biophys Acta 1774:93–101PubMed

15.

Chuthapisith S, Layfield R, Kerr ID, Hughes C, Eremin O (2007) Proteomic profiling of MCF-7 breast cancer cells with chemoresistance to different types of anti-cancer drugs. Int J Oncol 30:1545–1551PubMed

16.

Wilmes A, Bargh K, Kelly C, Northcote PT, Miller JH (2007) Peloruside A synergizes with other microtubule stabilizing agents in cultured cancer cell lines. Mol Pharmaceutics 4:269–280CrossRef

17.

Karp NA, Spencer M, Lindsay H, O’Dell K, Lilley KS (2005) Impact of replicate types on proteomic expression analysis. J Proteome Res 4:1867–1871PubMedCrossRef

18.

Young C, Truman P, Boucher M, Keyzers RA, Northcote P, Jordan TW (2009) The algal metabolite yessotoxin affects heterogeneous nuclear ribonucleoproteins in HepG2 cells. Proteomics 9:2529–2542PubMedCrossRef

19.

Peng L, Rawson P, McLauchlan D, Lehnert K, Snell R, Jordan TW (2008) Proteomic analysis of microsomes from lactating bovine mammary gland. J Proteome Res 7:1427–1432PubMedCrossRef

20.

Senthilnathan P, Padmanvathi R, Maqesh V, Sakthisekaran D (2006) Stabilization of membrane bound enzyme profiles and lipid peroxidation by Withania somnifera along with paclitaxel on benzo(a)pyrene induced experimental lung cancer. Cancer Sci 97:658–664PubMedCrossRef

21.

Verdier-Pinard P, Wang F, Martello L, Burd B, Orr GA, Horwitz SB (2003) Analysis of tubulin isotypes and mutations from taxol-resistant cells by combined isoelectrofocusing and mass spectrometry. Biochemistry 42:5349–5357PubMedCrossRef

22.

Burkhart CA, Kavallaris M, Horwitz SB (2001) The role of beta-tubulin isotypes in resistance to antimitotic drugs. Biochim Biophys Acta 1471:1–9

23.

Tommasi S, Mangia A, Lacalamita R, Bellizzi A, Fedele V, Chiriatti A, Thomssen C, Kendzierski N, Latorre A, Lorusso V, Schittulli F, Zito F, Kavallaris M, Paradiso A (2007) Cytoskeleton and paclitaxel sensitivity in breast cancer: the role of beta-tubulins. Int J Cancer 120:2078–2085PubMedCrossRef

24.

Ohishi Y, Oda Y, Basaki Y, Kobayashi H, Wake N, Kuwano M, Tsuneyoshi M (2007) Expression of beta-tubulin isotypes in human primary ovarian carcinoma. Gynecol Oncol 105:586–592PubMedCrossRef

25.

Marcus AI, Zhou J, O’Brate A, Hamel E, Wong J, Nivens M, El-Naggar A, Yao TP, Khuri FR, Giannakakou P (2005) The synergistic combination of the farnesyl transferase inhibitor lonafarnib and paclitaxel enhances tubulin acetylation and requires a functional tubulin deacetylase. Cancer Res 65:3883–3893PubMedCrossRef

26.

Westermann S, Weber K (2003) Post-translational modifications regulate microtubule function. Nat Rev Mol Cell Biol 4:938–947PubMedCrossRef

27.

Rubin CI, Atweh GF (2004) The role of stathmin in the regulation of the cell cycle. J Cell Biochem 93:242–250PubMedCrossRef

28.

Kozielski F, Skoufias DA, Indorato RL, Saoudi Y, Jungblut PR, Hustoft HK, Strozynski M, Thiede B (2008) Proteome analysis of apoptosis signaling by S-trityl-L-cysteine, a potent reversible inhibitor of human mitotic kinesin Eg5. Proteomics 8:289–300PubMedCrossRef

29.

Winkelmann I, Nässl AM, Daniel H, Wenzel U (2008) Proteome response in HT-29 human colorectal cancer cells to two apoptosis-inducing compounds with different mode of action. Int J Cancer 22:2223–2232CrossRef

30.

Curmi PA, Noguès C, Lachkar S, Carelle N, Gonthier MP, Sobel A, Liderau R, Bieche I (2000) Overexpression of stathmin in breast carcinomas points out to highly proliferative tumours. Br J Cancer 82:142–150PubMedCrossRef

31.

Yuan RH, Jeng YM, Chen HL, Lai PL, Pan HW, Hsieh FJ, Lin CY, Lee PH, Hsu HC (2006) Stathmin overexpression cooperates with p53 mutation and osteopontin overexpression, and is associated with tumour progression, early recurrence, and poor prognosis in hepatocellular carcinoma. J Pathol 209:549–558PubMedCrossRef

32.

Thome-Kromer B, Bonk I, Klatt M, Nebrich G, Taufmann M, Bryant S, Wacker U, Köpke A (2003) Towards the identification of liver toxicity markers: a proteome study in human cell culture and rats. Proteomics 3:1835–1862PubMedCrossRef

33.

Thiede B, Rudel T (2003) Proteome analysis of apoptotic cells. Mass Spectrom Rev 23:333–349CrossRef

34.

Carpenter B, MacKay C, Alnabulsi A, MacKay M, Telfer C, Melvin WT, Murray GI (2006) The roles of heterogeneous nuclear ribonucleoproteins in tumour development and progression. Biochim Biophys Acta 1765:85–100

35.

Holcik M, Gordon BW, Korneluk RG (2003) The internal ribosome entry site-mediated translation of antiapoptotic protein XIAP is modulated by the heterogeneous nuclear ribonucleoproteins C1 and C2. Mol Cell Biol 23:280–288PubMedCrossRef

36.

Patry C, Bouchard L, Labrecque P, Gendron D, Lemieux B, Toutant J, Lapointe E, Wellinger R, Chabot B (2003) Small interfering RNA-mediated reduction in heterogeneous nuclear ribonucleoparticule A1/A2 proteins induces apoptosis in human cancer cells but not in normal mortal cell lines. Cancer Res 63:7679–7688PubMed

37.

Revil T, Pelletier J, Toutant J, Cloutier A, Chabot B (2009) Heterogeneous nuclear ribonucleoprotein K represses the production of pro-apoptotic Bcl-xS splice isoform. J Biol Chem 284:21458–21467PubMedCrossRef

38.

Verrills NM, Walsh BJ, Cobon GS, Hains PG, Kavallaris M (2003) Proteome analysis of vinca alkaloid and resistance to acute lymphoblastic leukemia reveals novel cytoskeletal alterations. J Biol Chem 278:45082–45093PubMedCrossRef

39.

Crume KP, Miller JH, La Flamme AC (2007) Peloruside A, an anti-mitotic agent, specifically decreases TNF-α production by LPS-stimulated murine macrophages. Exp Biol Med 232:607–613

40.

Peiretti F, Bernot D, Lopez L, Bonardo B, Deprez-Beauclair P, Juhan-Vague I, Nalbone G (2003) Modulation of PAI-1 and proMMP-9 syntheses by soluble TNF and its receptors during differentiation of the human monocytic HL-60 cell line. J Cell Physiol 196:346–353PubMedCrossRef

41.

Stone JR, Collins T (2002) Rapid phosphorylation of heterogeneous nuclear ribonucleoprotein C1/C2 in response to physiologic levels of hydrogen peroxide in human endothelial cells. J Biol Chem 277:15621–15628PubMedCrossRef

42.

Villamarín S, Ferrer-Miralles N, Mansilla S, Priebe W, Portugal J (2002) Induction of G₂/M arrest and inhibition of c-myc and p53 transcription by WP631 in Jurkat T lymphocytes. Biochem Pharmacol 63:1251–1258PubMedCrossRef

43.

Gatti G, Maresca G, Natoli M, Florenzano F, Nicolin A, Felsani A, D’Agnano I (2009) Myc prevents apoptosis and enhances endoreduplication induced by paclitaxel. PLoS ONE 4:e5442PubMedCrossRef

44.

Menssen A, Epanchintsev A, Lodygin D, Rezaei N, Jung P, Verdoodt B, Diebold J, Hermeking H (2007) C-MYC delays prometaphase by direct transactivation of MAD2 and BubR1: identification of mechanisms underlying c-MYC-induced DNA damage and chromosomal instability. Cell Cycle 6:339–352PubMedCrossRef

45.

Ikui AE, Yang CP, Matsumoto T, Horwitz SB (2005) Low concentrations of taxol cause mitotic delay followed by premature dissociation of p55CDC from Mad2 and BubR1 and abrogation of the spindle checkpoint, leading to aneuploidy. Cell Cycle 4:1385–1388PubMedCrossRef

Title: Effects of the microtubule stabilizing agent peloruside A on the proteome of HL-60 cells
Authors: Anja Wilmes
Pisana Rawson
Lifeng Peng
Danyl McLauchlan
Peter T. Northcote
T. William Jordan
John H. Miller
Publication date: 01-08-2011
Publisher: Springer US
Published in: Investigational New Drugs / Issue 4/2011
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI: https://doi.org/10.1007/s10637-010-9387-5

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Summary

Please log in to get access to this content

Other articles of this Issue 4/2011

Baicalin induces human mucoepidermoid carcinoma Mc3 cells apoptosis in vitro and in vivo

Thioredxin reductase inhibitor ethaselen increases the drug sensitivity of the colon cancer cell line LoVo towards cisplatin via regulation of G1 phase and reversal of G2/M phase arrest

Phase II study of combination chemotherapy with irinotecan and cetuximab for pretreated metastatic colorectal cancer harboring wild-type KRAS

The anti-proliferative side effects of AEE788, a tyrosine kinase inhibitor blocking both EGF- and VEGF-receptor, are liver-size-dependent after partial hepatectomy in rats

A novel structural derivative of natural alkaloid ellipticine, MDPSQ, induces necrosis in leukemic cells

The notorious “drug lag” for oncology drugs in Japan

Keynote webinar | Spotlight on antibody–drug conjugates in cancer