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

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.

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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.

Item Type: Article
Funders: Aurigene Discovery Technologies (M) Sdn. Bhd., Universiti Malaya[RP027D15AFR], Universiti Malaya[PG038-2014A], Science and Technology Development Fund (STDF) Ministry of Higher Education & Scientific Research (MHESR)
Uncontrolled Keywords: BQR; DHODH; TAS-106; UCK2; Uridine abrogation
Subjects: R Medicine > RA Public aspects of medicine
Divisions: Faculty of Medicine
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 18 Apr 2022 03:13
Last Modified: 18 Apr 2022 03:59
URI: http://eprints.um.edu.my/id/eprint/26764

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