Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Triple Silencing of HSP27, cFLIP, and CLU Genes Promotes Sensitivity of Doxazosin-Induced Apoptosis in PC-3 Prostate Cancer Cells

Version 1 : Received: 8 January 2024 / Approved: 8 January 2024 / Online: 9 January 2024 (03:07:49 CET)

A peer-reviewed article of this Preprint also exists.

Cho, J.M.; Sun, S.; Im, E.; Yang, H.; Yoo, T.K. Triple Silencing of HSP27, cFLIP, and CLU Genes Promotes the Sensitivity of Doxazosin-Induced Apoptosis in PC-3 Prostate Cancer Cells. Medicines 2024, 11, 7. Cho, J.M.; Sun, S.; Im, E.; Yang, H.; Yoo, T.K. Triple Silencing of HSP27, cFLIP, and CLU Genes Promotes the Sensitivity of Doxazosin-Induced Apoptosis in PC-3 Prostate Cancer Cells. Medicines 2024, 11, 7.

Abstract

Background: This study investigated how the expression of heat shock protein 27 (HSP27), cellular FLICE-like inhibitory protein (cFLIP) and clusterin (CLU) affects the progression of cancer cells and their susceptibility to doxazosin-induced apoptosis. By silencing each of these genes individually, their effect on prostate cancer cell viability after doxazosin treatment was investigated. Methods: PC-3 prostate cancer cells were cultured and then subjected to gene silencing using siRNA targeting HSP27, cFLIP, and CLU, either individually, in pairs, or all together. Cells were then treated with doxazosin at various concentrations and their viability was assessed by MTT assay. Results: The study found that silencing the CLU gene in PC-3 cells significantly reduced cell viability after treatment with 25 µM doxazosin. In addition, dual silencing of cFLIP and CLU decreased cell viability at 10 µM doxazosin. Notably, silencing all three genes of HSP27, cFLIP, CLU was most effective and reduced cell viability even at a lower doxazosin concentration of 1 µM. Conclusions: Taken together, these findings suggest that simultaneous silencing of HSP27, cFLIP, and CLU genes may be a potential strategy to promote apoptosis in prostate cancer cells, which could inform future research on treatments for malignant prostate cancer.

Keywords

Apoptosis; CLU; cFLIP; Doxazosin; HSP27; Prostate cancer

Subject

Biology and Life Sciences, Cell and Developmental Biology

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