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A preliminary study on the impact of UCK2 knockdown in DLD-1 colorectal cells treated with DHODH inhibitor

Brequinar sodium ( BQR) is a well-studied inhibitor of the dihydroorotate dehydrogenase (DHODH) enzyme. Both the DHODH and uridine-cytidine kinase 2 (UCK2) enzymes have been reported to be over-expressed in cancer cells to maintain the cells high demand for DNA and RNA for their proliferation. In th...

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Main Authors: Kadir, Mohamad Fairus Abdul, Abdul-Rahman, Puteri Shafinaz Akmar, Nellore, Kavitha, Othman, Shatrah
Format: Article
Published: Penerbit Universiti Kebangsaan Malaysia 2021
Subjects:
RA Public aspects of medicine
Online Access:http://eprints.um.edu.my/26764/
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spelling my.um.eprints.267642022-04-18T03:59:40Z http://eprints.um.edu.my/26764/ A preliminary study on the impact of UCK2 knockdown in DLD-1 colorectal cells treated with DHODH inhibitor Kadir, Mohamad Fairus Abdul Abdul-Rahman, Puteri Shafinaz Akmar Nellore, Kavitha Othman, Shatrah RA Public aspects of medicine Brequinar sodium ( BQR) is a well-studied inhibitor of the dihydroorotate dehydrogenase (DHODH) enzyme. Both the DHODH and uridine-cytidine kinase 2 (UCK2) enzymes have been reported to be over-expressed in cancer cells to maintain the cells high demand for DNA and RNA for their proliferation. In this study, we aim to further sensitize cells to the effects of BQR by knocking down the UCK2 activity. In DLD-1 UCK2 knockdown cells, no change in the sensitivity of cells to BQR was observed. Uridine is known to reverse the anti-proliferative effect of DHODH inhibitors via the salvage pathway. We observed abrogation of approximately 30% of the uridine reversal effect in UCK2 knockdown cells compared to the wild type cells. Our finding indicates that the loss of UCK2 activity in the salvage pathway did not enhance the BQR-mediated cell proliferation inhibition but it abrogates the uridine reversal in the cells. Penerbit Universiti Kebangsaan Malaysia 2021-07 Article PeerReviewed Kadir, Mohamad Fairus Abdul and Abdul-Rahman, Puteri Shafinaz Akmar and Nellore, Kavitha and Othman, Shatrah (2021) A preliminary study on the impact of UCK2 knockdown in DLD-1 colorectal cells treated with DHODH inhibitor. Sains Malaysiana, 50 (7). pp. 1935-1946. ISSN 0126-6039, DOI https://doi.org/10.17576/jsm-2021-5007-09 <https://doi.org/10.17576/jsm-2021-5007-09>. 10.17576/jsm-2021-5007-09
institution Universiti Malaya
building UM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaya
content_source UM Research Repository
url_provider http://eprints.um.edu.my/
topic RA Public aspects of medicine
spellingShingle RA Public aspects of medicine
Kadir, Mohamad Fairus Abdul
Abdul-Rahman, Puteri Shafinaz Akmar
Nellore, Kavitha
Othman, Shatrah
A preliminary study on the impact of UCK2 knockdown in DLD-1 colorectal cells treated with DHODH inhibitor
description Brequinar sodium ( BQR) is a well-studied inhibitor of the dihydroorotate dehydrogenase (DHODH) enzyme. Both the DHODH and uridine-cytidine kinase 2 (UCK2) enzymes have been reported to be over-expressed in cancer cells to maintain the cells high demand for DNA and RNA for their proliferation. In this study, we aim to further sensitize cells to the effects of BQR by knocking down the UCK2 activity. In DLD-1 UCK2 knockdown cells, no change in the sensitivity of cells to BQR was observed. Uridine is known to reverse the anti-proliferative effect of DHODH inhibitors via the salvage pathway. We observed abrogation of approximately 30% of the uridine reversal effect in UCK2 knockdown cells compared to the wild type cells. Our finding indicates that the loss of UCK2 activity in the salvage pathway did not enhance the BQR-mediated cell proliferation inhibition but it abrogates the uridine reversal in the cells.
format Article
author Kadir, Mohamad Fairus Abdul
Abdul-Rahman, Puteri Shafinaz Akmar
Nellore, Kavitha
Othman, Shatrah
author_facet Kadir, Mohamad Fairus Abdul
Abdul-Rahman, Puteri Shafinaz Akmar
Nellore, Kavitha
Othman, Shatrah
author_sort Kadir, Mohamad Fairus Abdul
title A preliminary study on the impact of UCK2 knockdown in DLD-1 colorectal cells treated with DHODH inhibitor
title_short A preliminary study on the impact of UCK2 knockdown in DLD-1 colorectal cells treated with DHODH inhibitor
title_full A preliminary study on the impact of UCK2 knockdown in DLD-1 colorectal cells treated with DHODH inhibitor
title_fullStr A preliminary study on the impact of UCK2 knockdown in DLD-1 colorectal cells treated with DHODH inhibitor
title_full_unstemmed A preliminary study on the impact of UCK2 knockdown in DLD-1 colorectal cells treated with DHODH inhibitor
title_sort preliminary study on the impact of uck2 knockdown in dld-1 colorectal cells treated with dhodh inhibitor
publisher Penerbit Universiti Kebangsaan Malaysia
publishDate 2021
url http://eprints.um.edu.my/26764/
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score 13.211869

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