Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Cancer Cell International
Published in: Cancer Cell International 1/2011

Open Access 01-12-2011 | Primary research

Decreased therapeutic effects of noscapine combined with imatinib mesylate on human glioblastoma in vitro and the effect of midkine

Authors: Mine Erguven, Ayhan Bilir, Nuray Yazihan, Ezgi Ermis, Akin Sabanci, Esin Aktas, Yavuz Aras, Vehbi Alpman

Published in: Cancer Cell International | Issue 1/2011

Login to get access

Abstract

Background

Glioblastoma (GBM) develops resistance to the advances in chemotherapy leading to poor prognosis and life quality. Consequently, new treatment modalities are needed. Our aims were to investigate the effects of combined noscapine (NOS) and imatinib mesylate (IM) on human GBM in vitro and the role of midkine (MK) in this new combination treatment.

Methods

Monolayer and spheroid cultures of T98G human GBM cell line were used to evaluate the effects of IM (10 μM), Nos (10 μM) and their combination on cell proliferation and apoptotic indexes, cell cycle, the levels of antiapoptotic MK, MRP-1, p170, PFGFR-α, EGFR, bcl-2 proteins, apoptotic caspase-3 levels, morphology (SEM) and ultrastructure (TEM) for 72 hrs. Results were statistically analyzed using the Student's t-test.

Results

The combination group induced highest decrease in cell proliferation and apoptotic indexes, caspase-3 levels, MRP-1 and PDGFR-α levels. The decrease in p170 levels were lower than IM but higher that NOS. The highest increases were in EGFR, MK, bcl-2 and cAMP levels in the combination group. The G0+G1 cell cycle arrest at the end of 72nd hr was the lowest in the combination group. Apoptotic appearence was observed rarely both in the morphologic and ultrastructural evaluation of the combination group. In addition, autophagic vacuoles which were frequently observed in the IM group were observed rarely.

Conclusions

The combination of Nos with IM showed antagonist effect in T98G human GBM cells in vitro. This antagonist effect was correlated highly with MK levels. The effects of NOS on MRP-1, MK and receptor tyrosine kinase levels were firstly demonstrated in our report. In addition, we proposed that MK is one of the modulator in the switch of autophagy to cell death or survival/resistance.
Appendix
Available only for authorised users
Literature
1.
Furnari FB, Fenton T, Bachoo RM, Mukasa A, Stommel JM, Stegh A, Hahn WC, Ligon KL, Louis DN, Brennan C, Chin L, DePinho RA, Cavenee WK: Malignant astrocytic glioma: genetics, biology, and paths to treatment. Genes Dev. 2007, 21: 2683-2710. 10.1101/gad.1596707.CrossRefPubMed
2.
Zhou Q, Guo P, Gallo JM: Impact of angiogenesis inhibition by sunitinib on tumor distribution of temozolomide. Clin Cancer Rev. 2008, 14: 1540-1549. 10.1158/1078-0432.CCR-07-4544.CrossRef
3.
Bilir A, Erguven M, Yazihan N, Aktas E, Oktem G, Sabanci A: Enhancement of vinorelbine-induced cytotoxicity and apoptosis by clomipramine and lithium chloride in human neuroblastoma cancer cell line SH-SY5Y. J Neurooncol. 2010, 100: 385-395. 10.1007/s11060-010-0209-6.CrossRefPubMed
4.
Aneja R, Miyagi T, Karna P, Ezell T, Shukla D, Vij Gupta M, Yates C, Chinni SR, Zhau H, Chung LW, Joshi HC: A novel microtubule-modulating agent induces mitochondrially driven caspasedependent apoptosis via mitotic checkpoint activation in human prostate cancer cells. Eur J Cancer. 2010, 46: 1668-1678. 10.1016/j.ejca.2010.02.017.PubMedCentralCrossRefPubMed
5.
Zhou J, Gupta K, Yao J, Ye K, Panda D, Giannakakou P, Joshi HC: Paclitaxel-resistant human ovarian cancer cells undergo c-Jun NH2-terminal kinasemediated apoptosis in response to noscapine. J Biol Chem. 2002, 277: 39777-39785. 10.1074/jbc.M203927200.CrossRefPubMed
6.
De Vita S, De Matteis S, Laurenti L, Chiusolo P, Sorà F, Piccirillo N, Reddiconto G, Fiorini A, Leone G, Sica S: Imatinib for secondary Ph+ acute lymphoblastic leukemia induces response in concomitant GBM. Ann Oncol. 2006, 17: 720-721. 10.1093/annonc/mdj056.CrossRefPubMed
7.
Wen PY, Yung WK, Lamborn KR: Phase I/II study of imatinib mesylate for recurrent malignant gliomas: North American Brain Tumor Consortium Study 99-08. Clin Cancer Res. 2006, 12: 4899-4907. 10.1158/1078-0432.CCR-06-0773.CrossRefPubMed
8.
Bayraktar UD, Bayraktar S, Rocha-Lima CM: Molecular basis and management of gastrointestinal stromal tumors. World J Gastroenterol. 2010, 16: 2726-2734. 10.3748/wjg.v16.i22.2726.PubMedCentralCrossRefPubMed
9.
Ha HT, Lee JS, Urba S, Koenig RJ, Sisson J, Giordano T, Worden FP: A phase II study of imatinib in patients with advanced anaplastic thyroid cancer. Thyroid. 2010, 20: 975-980. 10.1089/thy.2010.0057.CrossRefPubMed
10.
Ustach CV, Huang W, Conley-LaComb MK, Lin CY, Che M, Abrams J, Kim HR: A Novel Signaling Axis of Matriptase/PDGF-D/{beta}-PDGFR in Human Prostate Cancer. Cancer Res. 2010
11.
Ranza E, Mazzini G, Facoetti A, Nano R: In-vitro effects of the tyrosine kinase inhibitor imatinib on glioblastoma cell proliferation. J Neurooncol. 2010, 96: 349-57. 10.1007/s11060-009-9975-4.CrossRefPubMed
12.
Bihorel S, Camenisch G, Lemaire M, Scherrmann JM: Influence of breast cancer resistance protein (Abcg2) and p-glycoprotein (Abcb1a) on the transport of imatinib mesylate (Gleevec) across the mouse blood-brain barrier. J Neurochem. 2007, 102: 1749-1757. 10.1111/j.1471-4159.2007.04808.x.CrossRefPubMed
13.
Reardon DA, Dresemann G, Taillibert S, Campone M, van den Bent M, Clement P, Blomquist E, Gordower L, Schultz H, Raizer J, Hau P, Easaw J, Gil M, Tonn J, Gijtenbeek A, Schlegel U, Bergstrom P, Green S, Weir A, Nikolova Z: Multicentre phase II studies evaluating imatinib plus hydroxyurea in patients with progressive glioblastoma. Br J Cancer. 2009, 101: 1995-2004. 10.1038/sj.bjc.6605411.PubMedCentralCrossRefPubMed
14.
Declèves X, Bihorel S, Debray M, Yousif S, Camenisch G, Scherrmann JM: ABC transporters and the accumulation of imatinib and its active metabolite CGP74588 in rat C6 glioma cells. Pharmacol Res. 2008, 57: 214-222. 10.1016/j.phrs.2008.01.006.CrossRefPubMed
15.
Muramatsu T: Midkine (MK), the product of a retinoic acid responsive gene, and pleiotrophin constitute a new protein family regulating growth and differentiation. Int J Dev Biol. 1993, 37: 183-8.PubMed
16.
Garver RI, Chan CS, Milner PG: Reciprocal expression of pleiotrophin and midkine in normal versus malignant lung tissues. Am J Respir Cell Mol Biol. 1993, 9: 463-466.CrossRefPubMed
17.
Garver RI, Radford DM, Donis-Keller H, Wick MR, Milner PG: Midkine and pleiotrophin expression in normal and malignant breast tissue. Cancer. 1994, 74: 1584-1590. 10.1002/1097-0142(19940901)74:5<1584::AID-CNCR2820740514>3.0.CO;2-V.CrossRefPubMed
18.
Konishi N, Nakamura M, Nakaoka S, Hiasa Y, Cho M, Uemura H, Hirao Y, Muramatsu T, Kadomatsu K: Immunohistochemical analysis of midkine expression in human prostate carcinoma. Oncology. 1999, 57: 253-257. 10.1159/000012039.CrossRefPubMed
19.
Ye C, Qi M, Fan QW, Ito K, Akiyama S, Kasai Y, Matsuyama M, Muramatsu T, Kadomatsu K: Expression of midkine in the early stage of carcinogenesis in human colorectal cancer. Br J Cancer. 1999, 79: 179-184. 10.1038/sj.bjc.6690030.PubMedCentralCrossRefPubMed
20.
Mishima K, Asai A, Kadomatsu K, Ino Y, Nomura K, Narita Y, Muramatsu T, Kirino T: Increased expression of midkine during the progression of human astrocytomas. Neurosci Lett. 1997, 233: 29-32. 10.1016/S0304-3940(97)00619-8.CrossRefPubMed
21.
Landen JW, Hau V, Wang M, Davis T, Ciliax B, Wainer BH, Van Meir EG, Glass JD, Joshi HC, Archer DR: Noscapine crosses the blood-brain barrier and inhibits glioblastoma growth. Clin Cancer Rev. 2004, 1: 5187-5201.CrossRef
22.
Newcomb EW, Lukyanov Y, Smirnova I, Schnee T, Zagzag D: Noscapine induces apoptosis in human glioma cells by an apoptosisinducing factor-dependent pathway. Anticancer Drug. 2008, 19: 553-563. 10.1097/CAD.0b013e3282ffd68d.CrossRef
23.
Erguven M, Yazihan N, Aktas E, Sabanci A, Li CJ, Oktem G, Bilir A: Carvedilol in glioma treatment alone and with imatinib in vitro. Int J Oncol. 2010, 36: 857-66.CrossRefPubMed
24.
Torres KE, Castillo G, Horwitz SB: Proc Am Assoc Cancer Res. 1997, 38: 530-
25.
Fan W, Miller MC, Cheng RL, Willingham MC: Induction of apoptosis by low concentrations of Taxol is not dependent on a G2/M block. Microsc Microanal. 1998, 4: 1042-1043.
26.
Miller MC, Johnson KR, Willingham MC, Fan W: Apoptotic cell death induced by baccatin III, a precursor of Taxol, occurs without G2/M arrest. Cancer Chemother Pharmacol. 1999, 44: 444-452. 10.1007/s002800051117.CrossRefPubMed
27.
Razis E, Selviaridis P, Labropoulos S, Norris JL, Zhu MJ, Song DD, Kalebic T, Torrens M, Kalogera-Fountzila A, Karkavelas G, Karanastasi S, Fletcher JA, Fountzilas G: Phase II study of neoadjuvant imatinib in glioblastoma: evaluation of clinical and molecular effects of the treatment. Clin Cancer Res. 2009, 15: 6258-6266. 10.1158/1078-0432.CCR-08-1867.CrossRefPubMed
28.
Ozawa T, Brennan CW, Wang L, Squatrito M, Sasayama T, Nakada M, Huse JT, Pedraza A, Utsuki S, Yasui Y, Tandon A, Fomchenko EI, Oka H, Levine RL, Fujii K, Ladanyi M, Holland EC: PDGFRA gene rearrangements are frequent genetic events in PDGFRAamplified glioblastomas. Genes Dev. 2010, 24: 2205-2218. 10.1101/gad.1972310.PubMedCentralCrossRefPubMed
29.
Spiegl-Kreinecker S, Buchroithner J, Elbling L, Steiner E, Wurm G, Bodenteich A, Fischer J, Micksche M, Berger W: Expression and functional activity of the ABC-transporter proteins P-glycoprotein and multidrug-resistance protein 1 in human brain tumor cells and astrocytes. J Neurooncol. 2002, 57: 27-36. 10.1023/A:1015735815111.CrossRefPubMed
30.
Mukai M, Che XF, Furukawa T, Sumizawa T, Aoki S, Ren XQ, Haraguchi M, Sugimoto Y, Kobayashi M, Takamatsu H, Akiyama S: Reversal of the resistance to STI571 in human chronic myelogenous leukemia K562 cells. Cancer Sci. 2003, 94: 557-563. 10.1111/j.1349-7006.2003.tb01482.x.CrossRefPubMed
31.
Maiuri MC, Le Toumelin G, Criollo A, Rain JC, Gautier F, Juin P, Tasdemir E, Pierron G, Troulinaki K, Tavernarakis N, Hickman JA, Geneste O, Kroemer G: Functional and physical interaction between Bcl-X(L) and a BH3-like domain in Beclin-1. EMBO J. 2007, 26: 2527-2539. 10.1038/sj.emboj.7601689.PubMedCentralCrossRefPubMed
32.
Zhivotovsky B, Orrenius S: Cell death mechanisms: cross-talk and role in disease. Exp Cell Res. 2010, 316: 1374-1383. 10.1016/j.yexcr.2010.02.037.CrossRefPubMed
33.
Bilir A, Erguven M, Oktem G, Ozdemir A, Uslu A, Aktas E, Bonavida B: Potentiation of cytotoxicity by combination of imatinib and chlorimipramine in glioma. Int J Oncol. 2008, 32: 829-839.PubMed
34.
Muramatsu T: Midkine, a heparin-binding cytokine with multiple roles in development, repair and diseases. Proc Jpn Acad Ser B Phys Biol Sci. 2010, 86: 410-425. 10.2183/pjab.86.410.PubMedCentralCrossRefPubMed
35.
Hu R, Yan Y, Li Q, Lin Y, Jin W, Li H, Lu Y, Pang T: Increased drug efflux along with midkine gene high expression in childhood B-lineage acute lymphoblastic leukemia cells. Int J Hematol. 2010, 92: 105-110. 10.1007/s12185-010-0613-x.CrossRefPubMed
Metadata
Title
Decreased therapeutic effects of noscapine combined with imatinib mesylate on human glioblastoma in vitro and the effect of midkine
Authors
Mine Erguven
Ayhan Bilir
Nuray Yazihan
Ezgi Ermis
Akin Sabanci
Esin Aktas
Yavuz Aras
Vehbi Alpman
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2011
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/1475-2867-11-18

Other articles of this Issue 1/2011

Cancer Cell International 1/2011 Go to the issue

Primary research

Expression and shedding of endothelial protein C receptor in prostate cancer cells

Primary research

Arsenic, cadmium and neuron specific enolase (ENO2, γ-enolase) expression in breast cancer

Primary research

Down-regulation of DcR2 sensitizes androgen-dependent prostate cancer LNCaP cells to TRAIL-induced apoptosis

Primary research

Chalcone-imidazolone conjugates induce apoptosis through DNA damage pathway by affecting telomeres

Primary research

A miRNA expression signature that separates between normal and malignant prostate tissues

Review

A short account of metastatic bone disease
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
Image Credits