Research Article
BibTex RIS Cite

Investigation of proapoptotic and anticancer effects mediated by intracellular ceramide changing dependent on ARN14974=BOC treatment in human non-small cell lung cancer

Year 2024, Volume: 17 Issue: 1, 36 - 48, 15.04.2024
https://doi.org/10.46309/biodicon.2023.1349188

Abstract

Sphingolipids are structural molecules of cellular membranes, that regulate biological processes such growth, proliferation, migration, metastasis by controlling signaling functions of cancer cells. Recent research in cancer therapy has sought to find mechanical details of tumor growth and roles of sphingolipids and their downstream targets in chemotherapy, radiotherapy and/or immunotherapy responses, by innovative molecular and pharmacological tools targeting sphingolipid signaling nodes in cancer cells.
Lung cancer is one of the most common cancers in our country and in the world. An important part of cancer-derived deaths is lung cancer-derived. New and effective treatment modalities for lung cancer are increasingly needed.
This research investigated the novel and effective treatment approach by inhibiting the formation of ceramidase-1-phosphate, which inhibits apoptosis, with synthesis of solid lipid nanoparticles of the ceramidase inhibitor-ARN14974=BOC, thereby increasing the intracellular level of cell and promoting cell viability and proliferation.
Results showed, cytotoxicity, antiproliferative effect, morphological and ultrastructural changes indicating apoptosis caused by ARN14974=BOC and its nanoparticle formulation on A549 cells. Apoptosis was induced by the agents via raising ROS, causing cell cycle arrest. The results underlined and prooved that cell death is trigered more effectively by the nanoparticle formulation of ARN14974=BOC on human non-small cell lung cancer cells.

Project Number

1901S014

References

  • [1] Parkin, D. M., Bray, F., Ferlay, J., & Pisani, P. (2002). Global cancer statistics. CA Cancer J Clin, 55(2), 74-108.
  • [2] Müsellim B. (2007). Akciğer kanserinin epidemiyolojisi ve etiyolojisi. Akciğer Kanserine Güncel Yaklaşım Sempozyum Dizisi 2007, 58, 113-118.
  • [3] Ogretmen B. (2018). Sphingolipid metabolism in cancer signalling and therapy. Nat Rev Cancer, 201818(1), 33-50.
  • [4] Pathwardhan G. A., & Liu, Y. Y. (2011). Sphingolipids and expression regulation of genes in cancer. Prog Lipid Res, 50(1), 104-114.
  • [5] Cuvillier O. (2002). Sphingosine in apoptosis signaling. Biochim Biophys Acta, 1585(2-3),153-162.
  • [6] Reynolds, D., Shi, B. J., McLean, C., Katsis, F., Kemp, B., & Dalton, S. (2003). Recruitment of Thr 319-phosphorylated Ndd1p to the FHA domain of Fkh2p requires Clb kinase activity: a mechanism for CLB cluster gene activation. Genes Dev., 17(14), 1789-802.
  • [7] Kolesnick, R. (2002). The therapeutic potential of modulating the ceramide/sphingomyelin pathway. J Clin Invest, 110(1), 3-8.
  • [8] Strelow. L., Janigro, D., & Nelson, J. A. (2002). Persistent SIV infection of a blood-brain barrier model. J Neurovirol., 8(4), 270-80.
  • [9] Rombaut, R., Dejonckheere, V., & Dewettinck, K. (2006). Microfiltration of butter serum upon casein micelle destabilization. J Dairy Sci, 89(6), 1915-25.
  • [10] Schmelz, E. M., Crall, K. J., Larocque, R., Dillehay, D. L., & Merrill, A. H. (1994). Uptake and metabolism of sphingolipids in isolated intestinal loops of mice. J Nutr, 124(5), 702-12.
  • [11] Saied, E. M., & Arenz, C. (2016). Inhibitors of ceramidases. Chem Phys Lipids., 197, 60-8.
  • [12] Oskouian, B., & Saba, J. D. (2010). Cancer treatment strategies targeting sphingolipid metabolism. Adv Exp Med Biol, 688, 185-205.
  • [13] Pizzirani, D., Bach, A., Realini, N., Armirotti, A., Mengatto, L., Bauer, I., Girotto, S., Pagliuca, C., De Vivo, M., Summa, M., Ribeiro, A., & Piomelli, D. (2015). Benzoxazolone carboxamides: potent and systemically active inhibitors of intracellular acid ceramidase. Angew Chem Int Ed Engl, 54(2), 485-9.
  • [14] Vejselova, D., Kutlu, H. M., Kus, G., Kabadere, S., & Uyar, R. (2014). Cytotoxic and apoptotic effects of ceranib-2 offering potential for a new antineoplastic agent in the treatment of cancer cells. Turk J Biol., 38, 916–921.
  • [15] Vejselova, D., Kutlu, H. M., & Kus, G. (2016). Examining impacts of ceranib-2 on the proliferation, morphology and ultrastructure of human breast cancer cells. Cytotechnology, 68, 2721–2728.
  • [16] Albayrak, M. & Kutlu, H. M. (2021). Investigation of apoptotic activities of NOE on human ovarian cancer cells . Biyolojik Çeşitlilik ve Koruma, 14 (1), 132-137.

ARN14974=BOC tedavisine bağlı intrasellüler seramid değişimi aracılı proapoptotik ve antikanser etkilerin insan küçük hücreli dışı akciğer kanserinde araştırılması

Year 2024, Volume: 17 Issue: 1, 36 - 48, 15.04.2024
https://doi.org/10.46309/biodicon.2023.1349188

Abstract

Sfingolipidler hücre membran yapısında bulunan ve kanser hücresinde sinyalleşme işlevlerini kontrol ederek büyüme, proliferasyon, göç, metastaz gibi biyolojik fonksiyonları düzenlemekte olan moleküllerdir. Kanser tedavisinde son yıllardaki araştırmalar, kanser hücrelerindeki sfingolipid sinyalleşmesini hedef alan, yenilikçi moleküler ve farmakolojik araçlar kullanılarak tümör büyümesinin ve kemoterapi, radyoterapi ve/veya immünoterapiye yanıtta sfingolipidlerin ve alt hedeflerinin rolü hakkında mekanik ayrıntılar bulmayı amaçlamıştır.
Akciğer kanseri ülkemizde ve dünyada en sık görülen kanser türlerindendir. Kanser kaynaklı ölümlerin önemli bir kısmı akciğer kanserine bağlıdır. Akciğer kanseri için yeni ve etkili tedavi yöntemlerinin geliştirilmesine her gün daha çok ihtiyaç duyulmaktadır.
Bu çalışmada, ARN14974=BOC seramidaz inhibitörünün katı lipit nanopartikül formunun sentezlenmesi ile seramidin hücre içi seviyesini arttırarak hücrenin yaşamını ve proliferasyonunu sağlayan ve apoptozu inhibe eden seramidaz-1-fosfatın oluşumunu engelleyerek yeni ve etkili bir tedavi yaklaşımının küçük hücreli dışı akciğer kanseri hücre hattı A549 hücrelerinde araştırılması amaçlanmıştır.
Çalışma sonuçları ARN14974=BOC’un ve nanopartikül formunun A549 hücrelerinde sitotoksik ve antiproliferatif etkileri tespit edilmiş ve bu hücrelerde apoptozu gösteren morfolojik ve ince yapısal değişiklikler saptanmıştır. Bu moleküllerin A549 hücrelerinde reaktif oksijen türlerinin artması ve hücre döngüsünün durdurulmasına neden olarak apoptozu tetiklemiştir. Bu sonuçlar, insan küçük hücreli dışı akciğer kanseri hücrelerinde hücre ölümünün sentezlenen ARN14974=BOC’un nanopartikül formu tarafından daha etkin bir biçimde gerçekleştirildiğini göstermiştir.

Supporting Institution

Anadolu Üniversitesi BAP

Project Number

1901S014

Thanks

Bu çalışma Anadolu Üniversitesi Bilimsel Araştırma Projeleri Kapsamında 1901S014 proje numarası ile desteklenmiştir.

References

  • [1] Parkin, D. M., Bray, F., Ferlay, J., & Pisani, P. (2002). Global cancer statistics. CA Cancer J Clin, 55(2), 74-108.
  • [2] Müsellim B. (2007). Akciğer kanserinin epidemiyolojisi ve etiyolojisi. Akciğer Kanserine Güncel Yaklaşım Sempozyum Dizisi 2007, 58, 113-118.
  • [3] Ogretmen B. (2018). Sphingolipid metabolism in cancer signalling and therapy. Nat Rev Cancer, 201818(1), 33-50.
  • [4] Pathwardhan G. A., & Liu, Y. Y. (2011). Sphingolipids and expression regulation of genes in cancer. Prog Lipid Res, 50(1), 104-114.
  • [5] Cuvillier O. (2002). Sphingosine in apoptosis signaling. Biochim Biophys Acta, 1585(2-3),153-162.
  • [6] Reynolds, D., Shi, B. J., McLean, C., Katsis, F., Kemp, B., & Dalton, S. (2003). Recruitment of Thr 319-phosphorylated Ndd1p to the FHA domain of Fkh2p requires Clb kinase activity: a mechanism for CLB cluster gene activation. Genes Dev., 17(14), 1789-802.
  • [7] Kolesnick, R. (2002). The therapeutic potential of modulating the ceramide/sphingomyelin pathway. J Clin Invest, 110(1), 3-8.
  • [8] Strelow. L., Janigro, D., & Nelson, J. A. (2002). Persistent SIV infection of a blood-brain barrier model. J Neurovirol., 8(4), 270-80.
  • [9] Rombaut, R., Dejonckheere, V., & Dewettinck, K. (2006). Microfiltration of butter serum upon casein micelle destabilization. J Dairy Sci, 89(6), 1915-25.
  • [10] Schmelz, E. M., Crall, K. J., Larocque, R., Dillehay, D. L., & Merrill, A. H. (1994). Uptake and metabolism of sphingolipids in isolated intestinal loops of mice. J Nutr, 124(5), 702-12.
  • [11] Saied, E. M., & Arenz, C. (2016). Inhibitors of ceramidases. Chem Phys Lipids., 197, 60-8.
  • [12] Oskouian, B., & Saba, J. D. (2010). Cancer treatment strategies targeting sphingolipid metabolism. Adv Exp Med Biol, 688, 185-205.
  • [13] Pizzirani, D., Bach, A., Realini, N., Armirotti, A., Mengatto, L., Bauer, I., Girotto, S., Pagliuca, C., De Vivo, M., Summa, M., Ribeiro, A., & Piomelli, D. (2015). Benzoxazolone carboxamides: potent and systemically active inhibitors of intracellular acid ceramidase. Angew Chem Int Ed Engl, 54(2), 485-9.
  • [14] Vejselova, D., Kutlu, H. M., Kus, G., Kabadere, S., & Uyar, R. (2014). Cytotoxic and apoptotic effects of ceranib-2 offering potential for a new antineoplastic agent in the treatment of cancer cells. Turk J Biol., 38, 916–921.
  • [15] Vejselova, D., Kutlu, H. M., & Kus, G. (2016). Examining impacts of ceranib-2 on the proliferation, morphology and ultrastructure of human breast cancer cells. Cytotechnology, 68, 2721–2728.
  • [16] Albayrak, M. & Kutlu, H. M. (2021). Investigation of apoptotic activities of NOE on human ovarian cancer cells . Biyolojik Çeşitlilik ve Koruma, 14 (1), 132-137.
There are 16 citations in total.

Details

Primary Language Turkish
Subjects Cell Development, Proliferation and Death, Traditional, Complementary and Integrative Medicine (Other)
Journal Section Research Articles
Authors

Gokhan Kus 0000-0002-2424-2720

Canan Vejselova Sezer 0000-0002-3792-5993

Ömer Koray Yaylacı 0000-0002-1846-9646

Emre Çömlekçi 0000-0002-7597-0381

Hatice Mehtap Kutlu 0000-0002-8816-1487

Project Number 1901S014
Early Pub Date January 18, 2024
Publication Date April 15, 2024
Submission Date August 24, 2023
Acceptance Date October 7, 2023
Published in Issue Year 2024 Volume: 17 Issue: 1

Cite

APA Kus, G., Vejselova Sezer, C., Yaylacı, Ö. K., Çömlekçi, E., et al. (2024). ARN14974=BOC tedavisine bağlı intrasellüler seramid değişimi aracılı proapoptotik ve antikanser etkilerin insan küçük hücreli dışı akciğer kanserinde araştırılması. Biological Diversity and Conservation, 17(1), 36-48. https://doi.org/10.46309/biodicon.2023.1349188

❖  Abstracted-Indexed in
Web of Science {Zoological Records Indexed] Clavariate Analytic, Medical Reads (RRS), CrossRef;10.46309/biodicon.

❖ Libraries
Aberystwyth University; All libraries; Bath University; Birmingham University; Cardiff University; City University London; CONSER (Not UK Holdings); Edinburgh University; Essex University; Exeter University; Eskişehir Technical University Library; EZB Electronic Journals Library; Feng Chia University Library; GAZİ Gazi University Library; Glasgow University; HEC-National Digital Library; Hull University; Imperial College London; Kaohsinug Medical University Library; ANKOS; Anadolu University Library; Lancaster University; Libros PDF; Liverpool University; London Metropolitan University; London School of Economics and Political Science; Manchester University; National Cheng Kung University Library; National ILAN University Library; Nottingham University; Open University; Oxford University; Queen Mary,University of London;Robert Gordon University; Royal Botanic Gardens, Kew; Sheffield Hallam University; Sheffield University; Shih Hsin University Library; Smithsonian Institution Libraries; Southampton University; Stirling University; Strathclyde University; Sussex University; The National Agricultural Library (NAL); The Ohio Library and Information NetWork; Trinity College Dublin; University of Washington Libraries; Vaughan Memorial Library; York University..

❖ The article processing is free.

❖ Web of Science-Clarivate Analytics, Zoological Record
❖ This journal is a CrossRef;10.46309/biodicon. member

❖ Please visit ” http:// www.biodicon.com“ ; "https://dergipark.org.tr/en/pub/biodicon"   for instructions about articles and all of the details about journal


❖  Correspondance Adres: Prof. Ersin YÜCEL, Sazova Mahallesi, Ziraat Caddesi, No.277 F Blok, 26005 Tepebaşı-Eskişehir/Türkiye
E-posta / E-mail: biodicon@gmail.com;
Web Address: http://www.biodicon.com;   https://dergipark.org.tr/en/pub/biodicon
❖ Biological Diversity and Conservation/ Biyolojik Çeşitlilik ve Koruma
❖ ISSN 1308-5301 Print; ISSN 1308-8084 Online
❖ Start Date Published 2008
© Copyright by Biological Diversity and Conservation/Biyolojik Çeşitlilik ve Koruma-Available online at www.biodicon.com/All rights reserved
Publisher : ERSİN YÜCEL (https://www.ersinyucel.com.tr/)
❖ This journal is published three numbers in a year. Printed in Eskişehir/Türkiye.
❖ All sorts of responsibilities of the articles published in this journal are belonging to the authors
Editör / Editor-In-Chief : Prof.Dr. Ersin YÜCEL, https://orcid.org/0000-0001-8274-7578