Inhibition of kinesin motor protein KIFC1 by AZ82 induces multipolar mitosis and apoptosis in prostate cancer cell

[Display omitted] •AZ82 inhibits transcription and translation of KIFC1 in prostate cancer (PCa) cells.•Inhibition of KIFC1 causes multipolar mitosis via de-clustering of extra centrosomes.•Loss of KIFC1 suppresses PCa cell proliferation by restricting cell cycle progression.•AZ82 causes PCa cell de...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Gene 2020-11, Vol.760, p.144989, Article 144989
Hauptverfasser: Parvin, Anzana, Hao, Shuang-Li, Tan, Fu-Qing, Yang, Wan-Xi
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:[Display omitted] •AZ82 inhibits transcription and translation of KIFC1 in prostate cancer (PCa) cells.•Inhibition of KIFC1 causes multipolar mitosis via de-clustering of extra centrosomes.•Loss of KIFC1 suppresses PCa cell proliferation by restricting cell cycle progression.•AZ82 causes PCa cell death through apoptosis. Kinesin 14 family member KIFC1 is a mitotic kinesin which contains a C-terminal motor domain and plays a vital role for clustering the amplified centrosomes. Overexpression of KIFC1 in prostate cancer (PCa) cells showed resistance to docetaxel (DTX). The present study revealed that small KIFC1 inhibitor AZ82 suppresed the transcription and translation of KIFC1 significantly in PCa cells. AZ82 inhibited the KIFC1 expression both in the cytoplasm and nucleus of PCa cells. Inhibition of KIFC1 by AZ82 caused multipolar mitosis in PCa cells via de-clustering the amplified centrosomes and decreased the rate of cancer cell growth and proliferation. Moreover, depletion of KIFC1 reduced cells entering the cell cycle and caused PCa cells death through apoptosis by increasing the expression of Bax and Cytochrome C. Thereby, KIFC1 silencing and inhibition decreased the PCa cells survival by inducing multipolar mitosis as well as apoptosis, suggesting inhibition of KIFC1 using AZ82 might be a strategy to treat PCa by controlling the cancer cell proliferation.
ISSN:0378-1119
1879-0038
DOI:10.1016/j.gene.2020.144989