Mechanisms of neuroblastoma cell growth inhibition by CARP-1 functional mimetics.

Neuroblastomas (NBs) are a clinically heterogeneous group of extra cranial pediatric tumors. Patients with high-risk, metastatic NBs have a long-term survival rate of below 40%, and are often resistant to current therapeutic modalities. Due to toxic side effects associated with radiation and chemoth...

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Main Authors:	Muthu, Magesh, Cheriyan, Vino T., Munie, Sara, Levi, Edi, Frank, John, Ashour, Abdelkader Elbadawy Abbas, Singh, Mandip, Rishi, Arun K.
Format:	Article
Language:	English English
Published:	The Public Library of Science 2014
Subjects:	RM300 Drugs and their action
Online Access:	http://irep.iium.edu.my/67281/ http://irep.iium.edu.my/67281/ http://irep.iium.edu.my/67281/ http://irep.iium.edu.my/67281/1/Mechanisms%20of%20Neuroblastoma%20Cell%20Growth%20Inhibition%20by%20CARP-1%20Functional%20Mimetics.pdf http://irep.iium.edu.my/67281/7/67281_Scopus%20-%20Document%20details.pdf

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spelling	iium-672812019-01-06T08:16:17Z http://irep.iium.edu.my/67281/ Mechanisms of neuroblastoma cell growth inhibition by CARP-1 functional mimetics. Muthu, Magesh Cheriyan, Vino T. Munie, Sara Levi, Edi Frank, John Ashour, Abdelkader Elbadawy Abbas Singh, Mandip Rishi, Arun K. RM300 Drugs and their action Neuroblastomas (NBs) are a clinically heterogeneous group of extra cranial pediatric tumors. Patients with high-risk, metastatic NBs have a long-term survival rate of below 40%, and are often resistant to current therapeutic modalities. Due to toxic side effects associated with radiation and chemotherapies, development of new agents is warranted to overcome resistance and effectively treat this disease in clinic. CARP-1 functional mimetics (CFMs) are an emerging class of small molecule compounds that inhibit growth of diverse cancer cell types. Here we investigated NB inhibitory potential of CFMs and the molecular mechanisms involved. CFM-1, -4, and -5 inhibited NB cell growth, in vitro, independent of their p53 and MYCN status. CFM-4 and -5 induced apoptosis in NB cells in part by activating pro-apoptotic stress-activated kinases (SAPKs) p38 and JNK, stimulating CARP-1 expression and cleavage of PARP1, while promoting loss of the oncogenes C and N-myc as well as mitotic cyclin B1. Treatments of NB cells with CFM-4 or -5 also resulted in loss of Inhibitory κB (IκB) α and β proteins. Micro-RNA profiling revealed upregulation of XIAP-targeting miR513a-3p in CFM-4-treated NB, mesothelioma, and breast cancer cells. Moreover, exposure of NB and breast cancer cells to CFM-4 or -5 resulted in diminished expression of anti-apoptotic XIAP1, cIAP1, and Survivin proteins. Expression of anti-miR513a-5p or miR513a-5p mimic, however, interfered with or enhanced, respectively, the breast cancer cell growth inhibition by CFM-4. CFMs also impacted biological properties of the NB cells by blocking their abilities to migrate, form colonies in suspension, and invade through the matrix-coated membranes. Our studies indicate anti-NB properties of CFM-4 and 5, and suggest that these CFMs and/or their future analogs have potential as anti-NB agents. The Public Library of Science 2014-07 Article PeerReviewed application/pdf en http://irep.iium.edu.my/67281/1/Mechanisms%20of%20Neuroblastoma%20Cell%20Growth%20Inhibition%20by%20CARP-1%20Functional%20Mimetics.pdf application/pdf en http://irep.iium.edu.my/67281/7/67281_Scopus%20-%20Document%20details.pdf Muthu, Magesh and Cheriyan, Vino T. and Munie, Sara and Levi, Edi and Frank, John and Ashour, Abdelkader Elbadawy Abbas and Singh, Mandip and Rishi, Arun K. (2014) Mechanisms of neuroblastoma cell growth inhibition by CARP-1 functional mimetics. PLoS One, 9 (7). pp. 1-17. E-ISSN 1932-6203 https://journals.plos.org/plosone/s/journal-information 10.1371/journal.pone.0102567
repository_type	Digital Repository
institution_category	Local University
institution	International Islamic University Malaysia
building	IIUM Repository
collection	Online Access
language	English English
topic	RM300 Drugs and their action
spellingShingle	RM300 Drugs and their action Muthu, Magesh Cheriyan, Vino T. Munie, Sara Levi, Edi Frank, John Ashour, Abdelkader Elbadawy Abbas Singh, Mandip Rishi, Arun K. Mechanisms of neuroblastoma cell growth inhibition by CARP-1 functional mimetics.
description	Neuroblastomas (NBs) are a clinically heterogeneous group of extra cranial pediatric tumors. Patients with high-risk, metastatic NBs have a long-term survival rate of below 40%, and are often resistant to current therapeutic modalities. Due to toxic side effects associated with radiation and chemotherapies, development of new agents is warranted to overcome resistance and effectively treat this disease in clinic. CARP-1 functional mimetics (CFMs) are an emerging class of small molecule compounds that inhibit growth of diverse cancer cell types. Here we investigated NB inhibitory potential of CFMs and the molecular mechanisms involved. CFM-1, -4, and -5 inhibited NB cell growth, in vitro, independent of their p53 and MYCN status. CFM-4 and -5 induced apoptosis in NB cells in part by activating pro-apoptotic stress-activated kinases (SAPKs) p38 and JNK, stimulating CARP-1 expression and cleavage of PARP1, while promoting loss of the oncogenes C and N-myc as well as mitotic cyclin B1. Treatments of NB cells with CFM-4 or -5 also resulted in loss of Inhibitory κB (IκB) α and β proteins. Micro-RNA profiling revealed upregulation of XIAP-targeting miR513a-3p in CFM-4-treated NB, mesothelioma, and breast cancer cells. Moreover, exposure of NB and breast cancer cells to CFM-4 or -5 resulted in diminished expression of anti-apoptotic XIAP1, cIAP1, and Survivin proteins. Expression of anti-miR513a-5p or miR513a-5p mimic, however, interfered with or enhanced, respectively, the breast cancer cell growth inhibition by CFM-4. CFMs also impacted biological properties of the NB cells by blocking their abilities to migrate, form colonies in suspension, and invade through the matrix-coated membranes. Our studies indicate anti-NB properties of CFM-4 and 5, and suggest that these CFMs and/or their future analogs have potential as anti-NB agents.
format	Article
author	Muthu, Magesh Cheriyan, Vino T. Munie, Sara Levi, Edi Frank, John Ashour, Abdelkader Elbadawy Abbas Singh, Mandip Rishi, Arun K.
author_facet	Muthu, Magesh Cheriyan, Vino T. Munie, Sara Levi, Edi Frank, John Ashour, Abdelkader Elbadawy Abbas Singh, Mandip Rishi, Arun K.
author_sort	Muthu, Magesh
title	Mechanisms of neuroblastoma cell growth inhibition by CARP-1 functional mimetics.
title_short	Mechanisms of neuroblastoma cell growth inhibition by CARP-1 functional mimetics.
title_full	Mechanisms of neuroblastoma cell growth inhibition by CARP-1 functional mimetics.
title_fullStr	Mechanisms of neuroblastoma cell growth inhibition by CARP-1 functional mimetics.
title_full_unstemmed	Mechanisms of neuroblastoma cell growth inhibition by CARP-1 functional mimetics.
title_sort	mechanisms of neuroblastoma cell growth inhibition by carp-1 functional mimetics.
publisher	The Public Library of Science
publishDate	2014
url	http://irep.iium.edu.my/67281/ http://irep.iium.edu.my/67281/ http://irep.iium.edu.my/67281/ http://irep.iium.edu.my/67281/1/Mechanisms%20of%20Neuroblastoma%20Cell%20Growth%20Inhibition%20by%20CARP-1%20Functional%20Mimetics.pdf http://irep.iium.edu.my/67281/7/67281_Scopus%20-%20Document%20details.pdf
first_indexed	2023-09-18T21:35:33Z
last_indexed	2023-09-18T21:35:33Z
_version_	1777412796047163392

Mechanisms of neuroblastoma cell growth inhibition by CARP-1 functional mimetics.

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