Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Research Article

Cytotoxic Impact of N-Oleoylethanolamine on Bone Cancer Cells

Author(s): Hüseyin İzgördü*, Canan Vejselova Sezer, Kadir Bayçelebi, Murat Baloğlu and Hatice Mehtap Kutlu

Volume 22, Issue 6, 2022

Published on: 17 June, 2021

Page: [1119 - 1123] Pages: 5

DOI: 10.2174/1871520621666210617091138

Price: $65

Abstract

Background: Cancer is a complex disease that derives from the uncontrolled proliferation of cells. Bone cancer is a type of prevalent cancer that occurs both in young and adults. Bone cancer is most common in the long bones of the pelvis, arms and legs. Statistically, more than 200 cases of osteosarcoma have been reported annually in our country. Classical treatment with chemotherapeutics remains ineffective in the cure of this cancer type. Recent studies have shown that ceramide induces apoptosis at its increased levels in the cells. Thus, many studies have been conducted to cause the accumulation of ceramide molecules in the cell by different ways to induce apoptosis. NOE (Noleoylethanolamine) is a specific inhibitor of ceramidase enzymes that hydrolyze intracellular ceramides and prevent apoptosis.

Objective: This study investigates the cytotoxic and apoptosis-inducing activities of NOE on human osteosarcoma Saos-2 cells.

Methods: Cytotoxic effects were investigated by MTT colorimetric assay. For the detection of morphological and ultrastructural indicators of apoptosis, confocal and TEM techniques were used.

Results: Our finding indicated that NOE is effective in the inhibition of the growth of Saos-2 cells. Confocal and TEM findings showed morphological and ultrastructural changes as chromatin condensation, fragmentation of nuclei and mitochondria as well as damaged cytoskeleton and cell shrinkage.

Conclusion: The results revealed that NOE exerts its cytotoxicity on Saos-2 cells through changing the ultrastructure and morphology of cells with clear apoptotic sparks.

Keywords: Cancer, apoptosis, osteosarcoma, N-oleoylethanolamine, sphingolipids, ceramidases, cytotoxicity.

Graphical Abstract

[1]
Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2015. CA Cancer J. Clin., 2015, 65(1), 5-29.
[http://dx.doi.org/10.3322/caac.21254] [PMID: 25559415]
[2]
Bankaoğlu, M.; Çiçek, E.D.; Cenker, M.; Eren, T.; Başak, M. Malign kemik tümörlerinin görüntülenmesinde radyolojik modaliteler; Şeh Tıp Bülteni, 2004, pp. 38-3.
[3]
Bielack, S.S.; Kempf-Bielack, B.; Delling, G.; Exner, G.U.; Flege, S.; Helmke, K.; Kotz, R.; Salzer-Kuntschik, M.; Werner, M.; Winkelmann, W.; Zoubek, A.; Jürgens, H.; Winkler, K. Prognostic factors in high-grade osteosarcoma of the extremities or trunk: An analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J. Clin. Oncol., 2002, 20(3), 776-790.
[http://dx.doi.org/10.1200/JCO.2002.20.3.776] [PMID: 11821461]
[4]
Mirabello, L.; Troisi, R.J.; Savage, S.A. Osteosarcoma incidence and survival rates from 1973 to 2004: Data from the surveillance, epidemiology, and end results program. Cancer, 2009, 115(7), 1531-1543.
[http://dx.doi.org/10.1002/cncr.24121] [PMID: 19197972]
[5]
Akşit, H.; Bildik, A. Apoptozis Yüzüncü yıl Üniversitesi Veterinerlik Fakültesi Dergisi, 2008, 19(1), 55-63.
[6]
Karttunen, M.; Haataja, M.P.; Säily, M.; Vattulainen, I.; Holopainen, J.M. Lipid domain morphologies in phosphatidylcholine-ceramide monolayers. Langmuir, 2009, 25(8), 4595-4600.
[http://dx.doi.org/10.1021/la803377s] [PMID: 19249826]
[7]
Hannun, Y.A.; Obeid, L.M. Many ceramides. J. Biol. Chem., 2011, 286(32), 27855-27862.
[http://dx.doi.org/10.1074/jbc.R111.254359] [PMID: 21693702]
[8]
Ogretmen, B. Sphingolipid metabolism in cancer signalling and therapy. Nat. Rev. Cancer, 2018, 18(1), 33-50.
[http://dx.doi.org/10.1038/nrc.2017.96] [PMID: 29147025]
[9]
Fogh, J.; Fogh, J.M.; Orfeo, T. One hundred and twenty-seven cultured human tumor cell lines producing tumors in nude mice. J. Natl. Cancer Inst., 1977, 59(1), 221-226.
[http://dx.doi.org/10.1093/jnci/59.1.221] [PMID: 327080]
[10]
Hausser, H.J.; Brenner, R.E. Phenotypic instability of Saos-2 cells in long-term culture. Biochem. Biophys. Res. Commun., 2005, 333(1), 216-222.
[http://dx.doi.org/10.1016/j.bbrc.2005.05.097] [PMID: 15939397]
[11]
Saied, E.M.; Arenz, C. Small molecule inhibitors of ceramidases. Cell. Physio. Biochem.: Int. J. Exp. Cell. Physio. Biochem. Pharmacol., 2014, 34(1), 197-212.
[12]
Cho, S.M.; Kwon, H.J. Acid ceramidase, an emerging target for anti-cancer and anti-angiogenesis. Arch. Pharm. Res., 2019, 42(3), 232-243.
[http://dx.doi.org/10.1007/s12272-019-01114-3] [PMID: 30661200]
[13]
Sakamoto, J.; Hamada, C.; Rahman, M.; Kodaira, S.; Ito, K.; Nakazato, H.; Ohashi, Y.; Yasutomi, M. An individual patient data meta-analysis of adjuvant therapy with carmofur in patients with curatively resected colon cancer. Japan J. Clin. Oncol., 2005, 35(9), 536-544.
[http://dx.doi.org/10.1093/jjco/hyi147] [PMID: 16155120]
[14]
Aliustaoğlu, M. Temel kanser fizyopatolojis. Klinik Gelişim Dergisi, 2009, 22(3), 46-49.
[15]
Aslan, G. Tümör immünolojisi. Turk J Immunol, 2010, 15(1), 7-13.
[16]
Klein, C.A. Cancer. The metastasis cascade. Science, 2008, 321(5897), 1785-1787.
[http://dx.doi.org/10.1126/science.1164853] [PMID: 18818347]
[17]
Bhabak, K.P.; Kleuser, B.; Huwiler, A.; Arenz, C. Effective inhibition of acid and neutral ceramidases by novel B-13 and LCL-464 analogues. Bioorg. Med. Chem., 2013, 21(4), 874-882.
[http://dx.doi.org/10.1016/j.bmc.2012.12.014] [PMID: 23312611]
[18]
İzgördü, H.; Vejselova Sezer, C.; Çömlekçi, E.; Kutlu, H.M. Characteristics of apoptosis induction in human breast cancer cells treated with a ceramidase inhibitor. Cytotechnology, 2020, 72(6), 907-919.
[http://dx.doi.org/10.1007/s10616-020-00436-1] [PMID: 33270814]
[19]
Yildiz-Ozer, M.; Oztopcu-Vatan, P.; Kus, G. The investigation of ceranib-2 on apoptosis and drug interaction with carboplatin in human non small cell lung cancer cells in vitro. Cytotechnology, 2018, 70(1), 387-396.
[http://dx.doi.org/10.1007/s10616-017-0154-8] [PMID: 29230631]
[20]
Vejselova, D.; Kutlu, H.M.; Kuş, G. Examining impacts of ceranib-2 on the proliferation, morphology and ultrastructure of human breast cancer cells. Cytotechnology, 2016, 68(6), 2721-2728.
[http://dx.doi.org/10.1007/s10616-016-9997-7] [PMID: 27380965]
[21]
Çömlekçi, E.; Kutlu, H.M.; Vejselova-Sezer, C. A new agent for the treatment of lung cancer: B13 loaded solid lipid nanoparticles Adv. Nat. Sci. Nanosci. Nanotechnol, 2020. 045014
[22]
Çömlekçi, E.; Vejselova-Sezer, C.; Kutlu, H.M. Handling a novel nanoscale d-erythro-MAPP in lung cancer treatment: An in vitro cytotoxicity research. Intl. J. Sci. Res. Biol. Sci., 2020, 7(4), 14-18.
[23]
Kus, G.; Kabadere, S.; Uyar, R.; Kutlu, H.M. Induction of apoptosis in prostate cancer cells by the novel ceramidase inhibitor ceranib-2. in vitro Cell. Dev. Biol. Anim., 2015, 51(10), 1056-1063.
[http://dx.doi.org/10.1007/s11626-015-9932-9] [PMID: 26170224]
[24]
Vethakanraj, H.S.; Sesurajan, B.P.; Padmanaban, V.P.; Jayaprakasam, M.; Murali, S.; Sekar, A.K. Anticancer effect of acid ceramidase inhibitor ceranib-2 in human breast cancer cell lines MCF-7, MDA MB-231 by the activation of SAPK/JNK, p38 MAPK apoptotic pathways, inhibition of the Akt pathway, downregulation of ERα. Anticancer Drugs, 2018, 29(1), 50-60.
[http://dx.doi.org/10.1097/CAD.0000000000000566] [PMID: 29023248]
[25]
Vejselova-Sezer, C.; Kutlu, H.M.; Kus, G.; Kabadere, S. UYAR, R. Cytotoxic and apoptotic effects of ceranib-2 offering potential for a new antineoplastic agent in the treatment of cancer cells. Turk. J. Biol., 2014, 38, 916-921.
[http://dx.doi.org/10.3906/biy-1405-36]
[26]
Draper, J.M.; Xia, Z.; Smith, R.A.; Zhuang, Y.; Wang, W.; Smith, C.D. İnsan seramidaz inhibitörlerinin keşfi ve değerlendirilmesi. Moleküler kanser terapötikleri, 2011, 10(11), 2052-2061.
[27]
Morales, A.; París, R.; Villanueva, A.; Llacuna, L.; García-Ruiz, C.; Fernández-Checa, J.C. Pharmacological inhibition or small interfering RNA targeting acid ceramidase sensitizes hepatoma cells to chemotherapy and reduces tumor growth in vivo. Oncogene, 2007, 26(6), 905-916.
[http://dx.doi.org/10.1038/sj.onc.1209834] [PMID: 16862171]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy