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Thymoquinone is a novel potential inhibitor of SIRT1 in cancers with p53 mutation: Role in the reactivation of tumor suppressor p73

  • Authors:
    • Mahmoud Alhosin
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  • Published online on: April 28, 2020     https://doi.org/10.3892/wasj.2020.49
  • ArticleNumber: 8
  • Copyright: © Alhosin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The deacetylase sirtuin 1 (SIRT1) has been shown to act as a negative regulator of the function of tumor suppressor p73 through a process involving the inhibition of the acetyltransferase p300 with the subsequent inhibition of apoptosis. In cancer cells with p53 mutation, such as the human acute lymphoblastic leukemia cell line (Jurkat) and the human triple-negative breast cancer (MDA-MB-468 cells), the upregulation of p73 in response to anticancer agents, including thymoquinone (TQ), leads to the activation of several pro-apoptotic genes with the subsequent induction of apoptosis. The present study investigated the effects of TQ on SIRT1 expression in order to elucidate the mechanisms of the TQ-induced upregulation of p73 in cancers with p53 mutation. TQ induced a dose and time-dependent decrease in SIRT1 expression in the Jurkat cells associated with the upregulation of p73, the cleavage of caspase-3, and the inhibition of cell proliferation and the induction of apoptosis. The TQ-induced downregulation of SIRT1 mRNA expression in Jurkat cells was associated with an increase in the mRNA expression of p300. In MDA-MB-468 cells, TQ induced an inhibition of cell proliferation and an upregulation of p300 and SIRT1 mRNA expression. Overall, the findings of the present study suggest that p73 is activated and stabilized in Jurkat cells in response to TQ via the deacetylation/acetylation-dependent pathway involving the downregulation of SIRT1 and the upregulation of p300, respectively. These findings further suggest that the inhibition of SIRT1 by TQ may be a promising strategy for the treatment of cancers with p53 mutation.
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July-August 2020
Volume 2 Issue 4

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Spandidos Publications style
Alhosin M: Thymoquinone is a novel potential inhibitor of SIRT1 in cancers with p53 mutation: Role in the reactivation of tumor suppressor p73. World Acad Sci J 2: 8, 2020
APA
Alhosin, M. (2020). Thymoquinone is a novel potential inhibitor of SIRT1 in cancers with p53 mutation: Role in the reactivation of tumor suppressor p73. World Academy of Sciences Journal, 2, 8. https://doi.org/10.3892/wasj.2020.49
MLA
Alhosin, M."Thymoquinone is a novel potential inhibitor of SIRT1 in cancers with p53 mutation: Role in the reactivation of tumor suppressor p73". World Academy of Sciences Journal 2.4 (2020): 8.
Chicago
Alhosin, M."Thymoquinone is a novel potential inhibitor of SIRT1 in cancers with p53 mutation: Role in the reactivation of tumor suppressor p73". World Academy of Sciences Journal 2, no. 4 (2020): 8. https://doi.org/10.3892/wasj.2020.49