Novel derivative of aminobenzenesulfonamide (3c) induces apoptosis in colorectal cancer cells through ROS generation and inhibits cell migration

Background: Colorectal cancer (CRC) is the 3rd most common type of cancer worldwide. New anti-cancer agents are needed for treating late stage colorectal cancer as most of the deaths occur due to cancer metastasis. A recently developed compound, 3c has shown to have potent antitumor effect; howeve...

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Main Authors:	Al-Khayal, Khayal A., Alafeefy, Ahmed Mahmoud, Vaali-Mohammed, Mansoor Ali, Mahmood, Amer A., Zubaidi, Ahmad Mohmmad, Al-Obeed, Omar A., Khan, Zahid, Abdulla, Maha Hamadien, Ahmad, Rehan
Format:	Article
Language:	English English English
Published:	BioMed Central 2017
Subjects:	RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Online Access:	http://irep.iium.edu.my/56359/ http://irep.iium.edu.my/56359/ http://irep.iium.edu.my/56359/ http://irep.iium.edu.my/56359/2/56359-Novel%20derivative%20of%20aminobenzenesulfonamide.pdf http://irep.iium.edu.my/56359/1/56359-Novel%20derivative%20of%20aminobenzenesulfonamide_SCOPUS.pdf http://irep.iium.edu.my/56359/3/56359-Novel%20derivative%20of%20aminobenzenesulfonamide_WOS.pdf

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spelling	iium-563592018-03-09T06:21:51Z http://irep.iium.edu.my/56359/ Novel derivative of aminobenzenesulfonamide (3c) induces apoptosis in colorectal cancer cells through ROS generation and inhibits cell migration Al-Khayal, Khayal A. Alafeefy, Ahmed Mahmoud Vaali-Mohammed, Mansoor Ali Mahmood, Amer A. Zubaidi, Ahmad Mohmmad Al-Obeed, Omar A. Khan, Zahid Abdulla, Maha Hamadien Ahmad, Rehan RC0254 Neoplasms. Tumors. Oncology (including Cancer) Background: Colorectal cancer (CRC) is the 3rd most common type of cancer worldwide. New anti-cancer agents are needed for treating late stage colorectal cancer as most of the deaths occur due to cancer metastasis. A recently developed compound, 3c has shown to have potent antitumor effect; however the mechanism underlying the antitumor effect remains unknown. Methods: 3c-induced inhibition of proliferation was measured in the absence and presence NAC using MTT in HT-29 and SW620 cells and xCELLigence RTCA DP instrument. 3c-induced apoptotic studies were performed using flow cytometry. 3c-induced redox alterations were measured by ROS production using fluorescence plate reader and flow cytometry and mitochondrial membrane potential by flow cytometry; NADPH and GSH levels were determined by colorimetric assays. Bcl2 family protein expression and cytochrome c release and PARP activation was done by western blotting. Caspase activation was measured by ELISA. Cell migration assay was done using the real time xCELLigence RTCA DP system in SW620 cells and wound healing assay in HT-29. Results: Many anticancer therapeutics exert their effects by inducing reactive oxygen species (ROS). In this study, we demonstrate that 3c-induced inhibition of cell proliferation is reversed by the antioxidant, N-acetylcysteine, suggesting that 3c acts via increased production of ROS in HT-29 cells. This was confirmed by the direct measurement of ROS in 3c-treated colorectal cancer cells. Additionally, treatment with 3c resulted in decreased NADPH and glutathione levels in HT-29 cells. Further, investigation of the apoptotic pathway showed increased release of cytochrome c resulting in the activation of caspase-9, which in turn activated caspase-3 and −6. 3c also (i) increased p53 and Bax expression, (ii) decreased Bcl2 and BclxL expression and (iii) induced PARP cleavage in human colorectal cancer cells. Confirming our observations, NAC significantly inhibited induction of apoptosis, ROS production, cytochrome c release and PARP cleavage. The results further demonstrate that 3c inhibits cell migration by modulating EMT markers and inhibiting TGFβ-induced phosphorylation of Smad2 and Samd3. Conclusions: Our findings thus demonstrate that 3c disrupts redox balance in colorectal cancer cells and support the notion that this agent may be effective for the treatment of colorectal cancer. BioMed Central 2017-01-03 Article PeerReviewed application/pdf en http://irep.iium.edu.my/56359/2/56359-Novel%20derivative%20of%20aminobenzenesulfonamide.pdf application/pdf en http://irep.iium.edu.my/56359/1/56359-Novel%20derivative%20of%20aminobenzenesulfonamide_SCOPUS.pdf application/pdf en http://irep.iium.edu.my/56359/3/56359-Novel%20derivative%20of%20aminobenzenesulfonamide_WOS.pdf Al-Khayal, Khayal A. and Alafeefy, Ahmed Mahmoud and Vaali-Mohammed, Mansoor Ali and Mahmood, Amer A. and Zubaidi, Ahmad Mohmmad and Al-Obeed, Omar A. and Khan, Zahid and Abdulla, Maha Hamadien and Ahmad, Rehan (2017) Novel derivative of aminobenzenesulfonamide (3c) induces apoptosis in colorectal cancer cells through ROS generation and inhibits cell migration. BMC Cancer, 17 (1). pp. 1-12. ISSN 1471-2407 https://bmccancer.biomedcentral.com/articles/10.1186/s12885-016-3005-7 10.1186/s12885-016-3005-7
repository_type	Digital Repository
institution_category	Local University
institution	International Islamic University Malaysia
building	IIUM Repository
collection	Online Access
language	English English English
topic	RC0254 Neoplasms. Tumors. Oncology (including Cancer)
spellingShingle	RC0254 Neoplasms. Tumors. Oncology (including Cancer) Al-Khayal, Khayal A. Alafeefy, Ahmed Mahmoud Vaali-Mohammed, Mansoor Ali Mahmood, Amer A. Zubaidi, Ahmad Mohmmad Al-Obeed, Omar A. Khan, Zahid Abdulla, Maha Hamadien Ahmad, Rehan Novel derivative of aminobenzenesulfonamide (3c) induces apoptosis in colorectal cancer cells through ROS generation and inhibits cell migration
description	Background: Colorectal cancer (CRC) is the 3rd most common type of cancer worldwide. New anti-cancer agents are needed for treating late stage colorectal cancer as most of the deaths occur due to cancer metastasis. A recently developed compound, 3c has shown to have potent antitumor effect; however the mechanism underlying the antitumor effect remains unknown. Methods: 3c-induced inhibition of proliferation was measured in the absence and presence NAC using MTT in HT-29 and SW620 cells and xCELLigence RTCA DP instrument. 3c-induced apoptotic studies were performed using flow cytometry. 3c-induced redox alterations were measured by ROS production using fluorescence plate reader and flow cytometry and mitochondrial membrane potential by flow cytometry; NADPH and GSH levels were determined by colorimetric assays. Bcl2 family protein expression and cytochrome c release and PARP activation was done by western blotting. Caspase activation was measured by ELISA. Cell migration assay was done using the real time xCELLigence RTCA DP system in SW620 cells and wound healing assay in HT-29. Results: Many anticancer therapeutics exert their effects by inducing reactive oxygen species (ROS). In this study, we demonstrate that 3c-induced inhibition of cell proliferation is reversed by the antioxidant, N-acetylcysteine, suggesting that 3c acts via increased production of ROS in HT-29 cells. This was confirmed by the direct measurement of ROS in 3c-treated colorectal cancer cells. Additionally, treatment with 3c resulted in decreased NADPH and glutathione levels in HT-29 cells. Further, investigation of the apoptotic pathway showed increased release of cytochrome c resulting in the activation of caspase-9, which in turn activated caspase-3 and −6. 3c also (i) increased p53 and Bax expression, (ii) decreased Bcl2 and BclxL expression and (iii) induced PARP cleavage in human colorectal cancer cells. Confirming our observations, NAC significantly inhibited induction of apoptosis, ROS production, cytochrome c release and PARP cleavage. The results further demonstrate that 3c inhibits cell migration by modulating EMT markers and inhibiting TGFβ-induced phosphorylation of Smad2 and Samd3. Conclusions: Our findings thus demonstrate that 3c disrupts redox balance in colorectal cancer cells and support the notion that this agent may be effective for the treatment of colorectal cancer.
format	Article
author	Al-Khayal, Khayal A. Alafeefy, Ahmed Mahmoud Vaali-Mohammed, Mansoor Ali Mahmood, Amer A. Zubaidi, Ahmad Mohmmad Al-Obeed, Omar A. Khan, Zahid Abdulla, Maha Hamadien Ahmad, Rehan
author_facet	Al-Khayal, Khayal A. Alafeefy, Ahmed Mahmoud Vaali-Mohammed, Mansoor Ali Mahmood, Amer A. Zubaidi, Ahmad Mohmmad Al-Obeed, Omar A. Khan, Zahid Abdulla, Maha Hamadien Ahmad, Rehan
author_sort	Al-Khayal, Khayal A.
title	Novel derivative of aminobenzenesulfonamide (3c) induces apoptosis in colorectal cancer cells through ROS generation and inhibits cell migration
title_short	Novel derivative of aminobenzenesulfonamide (3c) induces apoptosis in colorectal cancer cells through ROS generation and inhibits cell migration
title_full	Novel derivative of aminobenzenesulfonamide (3c) induces apoptosis in colorectal cancer cells through ROS generation and inhibits cell migration
title_fullStr	Novel derivative of aminobenzenesulfonamide (3c) induces apoptosis in colorectal cancer cells through ROS generation and inhibits cell migration
title_full_unstemmed	Novel derivative of aminobenzenesulfonamide (3c) induces apoptosis in colorectal cancer cells through ROS generation and inhibits cell migration
title_sort	novel derivative of aminobenzenesulfonamide (3c) induces apoptosis in colorectal cancer cells through ros generation and inhibits cell migration
publisher	BioMed Central
publishDate	2017
url	http://irep.iium.edu.my/56359/ http://irep.iium.edu.my/56359/ http://irep.iium.edu.my/56359/ http://irep.iium.edu.my/56359/2/56359-Novel%20derivative%20of%20aminobenzenesulfonamide.pdf http://irep.iium.edu.my/56359/1/56359-Novel%20derivative%20of%20aminobenzenesulfonamide_SCOPUS.pdf http://irep.iium.edu.my/56359/3/56359-Novel%20derivative%20of%20aminobenzenesulfonamide_WOS.pdf
first_indexed	2023-09-18T21:19:29Z
last_indexed	2023-09-18T21:19:29Z
_version_	1777411786007379968

Novel derivative of aminobenzenesulfonamide (3c) induces apoptosis in colorectal cancer cells through ROS generation and inhibits cell migration

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