Molecular mechanisms on how FABP5 inhibitors promote apoptosis-induction sensitivity of prostate cancer cells.



Zhang, Jiacheng, He, Gang, Jin, Xi, Alenezi, Bandar T, Naeem, Abdulghani A, Abdulsamad, Saud A and Ke, Youqiang ORCID: 0000-0001-5341-8644
(2023) Molecular mechanisms on how FABP5 inhibitors promote apoptosis-induction sensitivity of prostate cancer cells. Cell biology international, 47 (5). pp. 929-942.

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Abstract

Previous work showed that FABP5 inhibitors suppressed the malignant progression of prostate cancer cells, and this suppression might be achieved partially by promoting apoptosis. But the mechanisms involved were not known. Here, we investigated the effect of inhibitors on apoptosis and studied the relevant mechanisms. WtrFABP5 significantly reduced apoptotic cells in 22Rv1 and PC3 by 18% and 42%, respectively. In contrast, the chemical inhibitor SB-FI-26 produced significant increases in percentages of apoptotic cells in 22Rv1 and PC3 by 18.8% (±4.1) and 4.6% (±1.1), respectively. The bio- inhibitor dmrFABP5 also did so by 23.1% (±2.4) and 15.8% (±3.0), respectively, in these cell lines. Both FABP5 inhibitors significantly reduced the levels of the phosphorylated nuclear fatty acid receptor PPARγ, indicating that these inhibitors promoted apoptosis-induction sensitivity of the cancer cells by suppressing the biological activity of PPARγ. Thus, the phosphorylated PPARγ levels were reduced by FABP5 inhibitors, the levels of the phosphorylated AKT and activated nuclear factor kapper B (NFκB) were coordinately altered by additions of the inhibitors. These changes eventually led to the increased levels of cleaved caspase-9 and cleaved caspase-3; and thus, increase in the percentage of cells undergoing apoptosis. In untreated prostate cancer cells, increased FABP5 suppressed the apoptosis by increasing the biological activity of PPARγ, which, in turn, led to a reduced apoptosis by interfering with the AKT or NFκB signaling pathway. Our results suggested that the FABP5 inhibitors enhanced the apoptosis-induction of prostate cancer cells by reversing the biological effect of FABP5 and its related pathway.

Item Type: Article
Uncontrolled Keywords: AB-FI-26, apoptosis, dmrFABP5, FABP5, PPAR gamma, prostate cancer
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 30 Jan 2023 08:26
Last Modified: 08 Apr 2023 01:16
DOI: 10.1002/cbin.11989
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3167942