CARP-1 functional mimetic-4 is a novel suppressor of colorectal cancer cell growth and metastasis

ABSTRACT Background: Colorectal cancer (CRC) constitutes one of the most aggressive malignancies worldwide and in Malaysia. Due to high recurrence rate and toxic side effects of radiation and chemotherapies, new agents are urgently needed. CARP-1 is a peri-nuclear phospho-protein which plays a dy...

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Main Author:	Ashour, Abdelkader Elbadawy Abbas
Format:	Article
Language:	English English English
Published:	IIUM Press 2019
Subjects:	RM300 Drugs and their action
Online Access:	http://irep.iium.edu.my/78963/ http://irep.iium.edu.my/78963/ http://irep.iium.edu.my/78963/1/Certificate_of_Attendance%2026%20at%20KRD%202019.pdf http://irep.iium.edu.my/78963/2/KRD2019AbstractBook.pdf http://irep.iium.edu.my/78963/13/290-Article%20Text-1736-1-10-20200106.pdf

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recordtype	eprints
spelling	iium-789632020-02-27T07:33:10Z http://irep.iium.edu.my/78963/ CARP-1 functional mimetic-4 is a novel suppressor of colorectal cancer cell growth and metastasis Ashour, Abdelkader Elbadawy Abbas RM300 Drugs and their action ABSTRACT Background: Colorectal cancer (CRC) constitutes one of the most aggressive malignancies worldwide and in Malaysia. Due to high recurrence rate and toxic side effects of radiation and chemotherapies, new agents are urgently needed. CARP-1 is a peri-nuclear phospho-protein which plays a dynamic role in regulating cell growth and apoptosis. CARP-1 functional mimetics (CFMs) are a class of compounds that stimulate CARP-1. CFM-4, a lead compound, was shown to suppress growth and metastasis of various cancers. Purpose: To assess the extent to which CFM-4 inhibits CRC proliferation and metastasis and delineate the mechanism. Methodology: CFM-4 anti-cancer effects of on CRC cells were investigated using MTT assay, Annexin V/Propidium iodide (PI) apoptosis assay, cell cycle analysis, quantitative real-time PCR (qRT-PCR) and Western blotting. Antimetastatic activities were assessed by migration, colony formation and invasion assays. Results: CFM-4 inhibited CRC cell proliferation and was much more potent than the classical anti-CRC 5-fluorouracil. These effects were shown to be mediated at least in part by stimulating apoptosis, as indicated in our Annexin V/PI assay results. Cell cycle analysis showed that CFM-4 induced G2/M phase arrest. Molecularly, qRT-PCR results revealed that CFM-4 promoted intrinsic apoptosis by upregulating expression of caspase-8 and -9, p53, PUMA and Noxa, and stimulated extrinsic apoptosis by enhancing expression of death receptors. CFM-4 upregulated NF-B signaling inhibitor A20-binding inhibitor protein-1 and the PI3K negative regulator PTEN. Western blot analysis results revealed that CFM-4 enhanced expression of CARP-1, caspase-8 and executioner caspase-3. Metastatic properties of the CRC cells were reduced by CFM-4 through blocking their capabilities to form colonies, migrate and invade through the matrix-coated membranes. Conclusion: The potent antitumor and anti-metastatic properties of CFM-4 against CRC are due to collective pro-apoptotic, anti-proliferative and anti-metastatic activities. Together our data warrants further investigations of CFM-4 as potential anti-tumor agent for CRC malignancy and metastasis. IIUM Press 2019-11-27 Article PeerReviewed application/pdf en http://irep.iium.edu.my/78963/1/Certificate_of_Attendance%2026%20at%20KRD%202019.pdf application/pdf en http://irep.iium.edu.my/78963/2/KRD2019AbstractBook.pdf application/pdf en http://irep.iium.edu.my/78963/13/290-Article%20Text-1736-1-10-20200106.pdf Ashour, Abdelkader Elbadawy Abbas (2019) CARP-1 functional mimetic-4 is a novel suppressor of colorectal cancer cell growth and metastasis. International Journal of Allied Health Sciences, 3 (3). p. 741. E-ISSN 2600-8491 https://journals.iium.edu.my/ijahs/index.php/IJAHS/article/view/290
repository_type	Digital Repository
institution_category	Local University
institution	International Islamic University Malaysia
building	IIUM Repository
collection	Online Access
language	English English English
topic	RM300 Drugs and their action
spellingShingle	RM300 Drugs and their action Ashour, Abdelkader Elbadawy Abbas CARP-1 functional mimetic-4 is a novel suppressor of colorectal cancer cell growth and metastasis
description	ABSTRACT Background: Colorectal cancer (CRC) constitutes one of the most aggressive malignancies worldwide and in Malaysia. Due to high recurrence rate and toxic side effects of radiation and chemotherapies, new agents are urgently needed. CARP-1 is a peri-nuclear phospho-protein which plays a dynamic role in regulating cell growth and apoptosis. CARP-1 functional mimetics (CFMs) are a class of compounds that stimulate CARP-1. CFM-4, a lead compound, was shown to suppress growth and metastasis of various cancers. Purpose: To assess the extent to which CFM-4 inhibits CRC proliferation and metastasis and delineate the mechanism. Methodology: CFM-4 anti-cancer effects of on CRC cells were investigated using MTT assay, Annexin V/Propidium iodide (PI) apoptosis assay, cell cycle analysis, quantitative real-time PCR (qRT-PCR) and Western blotting. Antimetastatic activities were assessed by migration, colony formation and invasion assays. Results: CFM-4 inhibited CRC cell proliferation and was much more potent than the classical anti-CRC 5-fluorouracil. These effects were shown to be mediated at least in part by stimulating apoptosis, as indicated in our Annexin V/PI assay results. Cell cycle analysis showed that CFM-4 induced G2/M phase arrest. Molecularly, qRT-PCR results revealed that CFM-4 promoted intrinsic apoptosis by upregulating expression of caspase-8 and -9, p53, PUMA and Noxa, and stimulated extrinsic apoptosis by enhancing expression of death receptors. CFM-4 upregulated NF-B signaling inhibitor A20-binding inhibitor protein-1 and the PI3K negative regulator PTEN. Western blot analysis results revealed that CFM-4 enhanced expression of CARP-1, caspase-8 and executioner caspase-3. Metastatic properties of the CRC cells were reduced by CFM-4 through blocking their capabilities to form colonies, migrate and invade through the matrix-coated membranes. Conclusion: The potent antitumor and anti-metastatic properties of CFM-4 against CRC are due to collective pro-apoptotic, anti-proliferative and anti-metastatic activities. Together our data warrants further investigations of CFM-4 as potential anti-tumor agent for CRC malignancy and metastasis.
format	Article
author	Ashour, Abdelkader Elbadawy Abbas
author_facet	Ashour, Abdelkader Elbadawy Abbas
author_sort	Ashour, Abdelkader Elbadawy Abbas
title	CARP-1 functional mimetic-4 is a novel suppressor of colorectal cancer cell growth and metastasis
title_short	CARP-1 functional mimetic-4 is a novel suppressor of colorectal cancer cell growth and metastasis
title_full	CARP-1 functional mimetic-4 is a novel suppressor of colorectal cancer cell growth and metastasis
title_fullStr	CARP-1 functional mimetic-4 is a novel suppressor of colorectal cancer cell growth and metastasis
title_full_unstemmed	CARP-1 functional mimetic-4 is a novel suppressor of colorectal cancer cell growth and metastasis
title_sort	carp-1 functional mimetic-4 is a novel suppressor of colorectal cancer cell growth and metastasis
publisher	IIUM Press
publishDate	2019
url	http://irep.iium.edu.my/78963/ http://irep.iium.edu.my/78963/ http://irep.iium.edu.my/78963/1/Certificate_of_Attendance%2026%20at%20KRD%202019.pdf http://irep.iium.edu.my/78963/2/KRD2019AbstractBook.pdf http://irep.iium.edu.my/78963/13/290-Article%20Text-1736-1-10-20200106.pdf
first_indexed	2023-09-18T21:51:07Z
last_indexed	2023-09-18T21:51:07Z
_version_	1777413775986524160

CARP-1 functional mimetic-4 is a novel suppressor of colorectal cancer cell growth and metastasis

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