Viability of glioblastoma stem cells is effectively reduced by diisothiocyanate‑derived mercapturic acids

Cwiklowska,Kamila; Westhoff,Mike‑Andrew; Freisinger,Simon; Dwucet,Annika; Halatsch,Marc‑Eric; Knippschild,Uwe; Debatin,Klaus‑Michael; Schirmbeck,Reinhold; Winiarski,Lukasz; Oleksyszyn,Jozef; Wirtz,Christian Rainer; Burster,Timo

doi:10.3892/ol.2018.9347

Viability of glioblastoma stem cells is effectively reduced by diisothiocyanate‑derived mercapturic acids

Authors:
- Kamila Cwiklowska
- Mike‑Andrew Westhoff
- Simon Freisinger
- Annika Dwucet
- Marc‑Eric Halatsch
- Uwe Knippschild
- Klaus‑Michael Debatin
- Reinhold Schirmbeck
- Lukasz Winiarski
- Jozef Oleksyszyn
- Christian Rainer Wirtz
- Timo Burster
View Affiliations

Affiliations: Department of Neurosurgery, Surgery Center, Ulm University Medical Center, D‑89081 Ulm, Germany, Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, D‑89081 Ulm, Germany, Department of General and Visceral Surgery, Surgery Center, Ulm University Medical Center, D‑89081 Ulm, Germany, Internal Medicine I, Ulm University Medical Center, D‑89081 Ulm, Germany, Faculty of Chemistry, Wroclaw University of Technology, 50‑370 Wroclaw, Poland
Published online on: August 21, 2018 https://doi.org/10.3892/ol.2018.9347
Pages: 6181-6187

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Glioblastoma is the most aggressive tumor of the central nervous system and is manifested by diffuse invasion of glioblastoma stem cells into the healthy tissue, chemoresistance and recurrence. Despite aggressive therapy, consisting of maximal surgical resection, radiotherapy and chemotherapy with temozolomide (Temodal®), life expectancy of patients with glioblastoma is typically less than 15 months. In general, natural isothiocyanates isolated from plants of the Cruciferae family are selectively cytotoxic to tumor cells. It has been demonstrated previously that diisothiocyanate‑derived mercapturic acids are highly cytotoxic to colon cancer cells. In the present study, the application of diisothiocyanate‑derived mercapturic acids led to a decrease in the viability of an established glioblastoma cell line, primary patient‑derived sphere‑cultured stem cell‑enriched cell populations (SCs), and cells differentiated from SCs. Consequently, targeting glioblastoma cells by diisothiocyanate‑derived mercapturic acids is a promising approach to restrict tumor cell growth and may be a novel therapeutic intervention for the treatment of glioblastoma.

View Figures

View References

1	Jue TR and McDonald KL: The challenges associated with molecular targeted therapies for glioblastoma. J Neurooncol. 127:427–434. 2016. View Article : Google Scholar : PubMed/NCBI
2	Koukourakis MI, Mitrakas AG and Giatromanolaki A: Therapeutic interactions of autophagy with radiation and temozolomide in glioblastoma: Evidence and issues to resolve. Br J Cancer. 114:485–496. 2016. View Article : Google Scholar : PubMed/NCBI
3	Dinkova-Kostova AT and Kostov RV: Glucosinolates and isothiocyanates in health and disease. Trends Mol Med. 18:337–347. 2012. View Article : Google Scholar : PubMed/NCBI
4	Singh SV and Singh K: Cancer chemoprevention with dietary isothiocyanates mature for clinical translational research. Carcinogenesis. 33:1833–1842. 2012. View Article : Google Scholar : PubMed/NCBI
5	Trachootham D, Zhou Y, Zhang H, Demizu Y, Chen Z, Pelicano H, Chiao PJ, Achanta G, Arlinghaus RB, Liu J and Huang P: Selective killing of oncogenically transformed cells through a ROS-mediated mechanism by beta-phenylethyl isothiocyanate. Cancer Cell. 10:241–252. 2006. View Article : Google Scholar : PubMed/NCBI
6	Grzywa R, Winiarski Ł, Psurski M, Rudnicka A, Wietrzyk J, Gajda T and Oleksyszyn J: Synthesis and biological activity of diisothiocyanate-derived mercapturic acids. Bioorg Med Chem Lett. 26:667–671. 2016. View Article : Google Scholar : PubMed/NCBI
7	Schneider M, Ströbele S, Nonnenmacher L, Siegelin MD, Tepper M, Stroh S, Hasslacher S, Enzenmüller S, Strauss G, Baumann B, et al: A paired comparison between glioblastoma ‘stem cells’ and differentiated cells. Int J Cancer. 138:1709–1718. 2016. View Article : Google Scholar : PubMed/NCBI
8	Ströbele S, Schneider M, Schneele L, Siegelin MD, Nonnenmacher L, Zhou S, Karpel-Massler G, Westhoff MA, Halatsch ME and Debatin KM: A potential role for the inhibition of PI3K signaling in glioblastoma therapy. PLoS One. 10:e01316702015. View Article : Google Scholar : PubMed/NCBI
9	Westhoff MA, Zhou S, Bachem MG, Debatin KM and Fulda S: Identification of a novel switch in the dominant forms of cell adhesion-mediated drug resistance in glioblastoma cells. Oncogene. 27:5169–5181. 2008. View Article : Google Scholar : PubMed/NCBI
10	Cheng F, Li W, Zhou Y, Shen J, Wu Z, Liu G, Lee PW and Tang Y: admetSAR: A comprehensive source and free tool for evaluating chemical ADMET properties. J Chem Inf Model. 52:3099–3105. 2012. View Article : Google Scholar : PubMed/NCBI
11	Schneider M, Ströbele S, Nonnenmacher L, Siegelin MD, Tepper M, Stroh S, Hasslacher S, Enzenmüller S, Strauss G, Baumann B, et al: A paired comparison between glioblastoma ‘stem cells’ and differentiated cells. Int J Cancer. 138:1709–1718. 2016. View Article : Google Scholar : PubMed/NCBI
12	Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J and Dirks PB: Identification of a cancer stem cell in human brain tumors. Cancer Res. 63:5821–5828. 2003.PubMed/NCBI
13	Liu G, Yuan X, Zeng Z, Tunici P, Ng H, Abdulkadir IR, Lu L, Irvin D, Black KL and Yu JS: Analysis of gene expression and chemoresistance of CD133⁺ cancer stem cells in glioblastoma. Mol Cancer. 5:672006. View Article : Google Scholar : PubMed/NCBI
14	Jordan CT, Guzman ML and Noble M: Cancer stem cells. N Engl J Med. 355:1253–1261. 2006. View Article : Google Scholar : PubMed/NCBI
15	Jadhav U, Ezhilarasan R, Vaughn SF, Berhow MA and Mohanam S: Dietary isothiocyanate iberin inhibits growth and induces apoptosis in human glioblastoma cells. J Pharmacol Sci. 103:247–251. 2007. View Article : Google Scholar : PubMed/NCBI
16	Zhu Y, Liu A, Zhang X, Qi L, Zhang L, Xue J, Liu Y and Yang P: The effect of benzyl isothiocyanate and its computer-aided design derivants targeting alkylglycerone phosphate synthase on the inhibition of human glioma U87MG cell line. Tumour Biol. 36:3499–3509. 2015. View Article : Google Scholar : PubMed/NCBI
17	Tang NY, Chueh FS, Yu CC, Liao CL, Lin JJ, Hsia TC, Wu KC, Liu HC, Lu KW and Chung JG: Benzyl isothiocyanate alters the gene expression with cell cycle regulation and cell death in human brain glioblastoma GBM 8401 cells. Oncol Rep. 35:2089–2096. 2016. View Article : Google Scholar : PubMed/NCBI
18	Shang HS, Shih YL, Lu TJ, Lee CH, Hsueh SC, Chou YC, Lu HF, Liao NC and Chung JG: Benzyl isothiocyanate (BITC) induces apoptosis of GBM 8401 human brain glioblastoma multiforms cells via activation of caspase-8/bid and the reactive oxygen species-dependent mitochondrial pathway. Environmental Toxicology. 31:1751–1760. 2016. View Article : Google Scholar : PubMed/NCBI
19	Chou YC, Chang MY, Wang MJ, Harnod T, Hung CH, Lee HT, Shen CC and Chung JG: PEITC induces apoptosis of human brain glioblastoma GBM8401 cells through the extrinsic- and intrinsic -signaling pathways. Neurochem Int. 81:32–40. 2015. View Article : Google Scholar : PubMed/NCBI
20	Portnow J, Badie B, Chen M, Liu A, Blanchard S and Synold TW: The neuropharmacokinetics of temozolomide in patients with resectable brain tumors: Potential implications for the current approach to chemoradiation. Clin Cancer Res. 15:7092–7098. 2009. View Article : Google Scholar : PubMed/NCBI
21	Patel MA, Kim JE, Ruzevick J, Li G and Lim M: The future of glioblastoma therapy: Synergism of standard of care and immunotherapy. Cancers (Basel). 6:1953–1985. 2014. View Article : Google Scholar : PubMed/NCBI