TY  - JOUR
T1  - Activation of Caspase-1 by NLRP3 Inflammasome Drives Malignant Progression in Prostate Cancer
A1  - Grace Wanjiku Mwangi
A1  - Lucy Atieno Otieno
JF  - Archive of International Journal of Cancer and Allied Science
JO  - Arch Int J Cancer Allied Sci
SN  - 3108-4834
Y1  - 2025
VL  - 5
IS  - 2
DO  - 10.51847/1yhmTnQIyC
SP  - 125
EP  - 137
N2  - Inflammation is increasingly recognized as a key contributor to the onset and progression of prostate cancer (PCa). In this study, we investigated the molecular mechanisms by which the NLR family pyrin domain-containing protein 3 (NLRP3) inflammasome influences PCa malignancy. NLRP3 expression in PCa tissues and cell lines was measured using quantitative real-time PCR (qRT-PCR) and fluorescence in situ hybridization (FISH). To explore its functional role, we performed gain- and loss-of-function experiments in LNCaP and PC3 cells, assessing proliferation, apoptosis, and migration via TUNEL, CCK-8, and Transwell assays. The interplay between caspase-1 and NLRP3 was further examined through rescue experiments, western blotting, and qRT-PCR. In vivo, the tumor-promoting effects of NLRP3 were evaluated using a subcutaneous xenograft model.Our results revealed that NLRP3 expression was significantly elevated in PCa tissues and cell lines. Functionally, activation of the NLRP3/caspase-1 inflammasome by ATP+ LPS enhanced proliferation and migratory capacity while reducing apoptosis in PC3 and LNCaP cells. Western blot analysis confirmed increased caspase-1 activity following inflammasome activation. Overexpression of NLRP3 accelerated malignant behaviors, whereas silencing NLRP3 had the opposite effect, mediated at least in part through caspase-1. Rescue experiments demonstrated that modulating caspase-1 expression could reverse the effects of NLRP3 overexpression or knockdown, establishing a regulatory link between the two proteins. Consistently, NLRP3 depletion in vivo significantly impaired tumor growth. Overall, these findings highlight the critical role of the NLRP3 inflammasome in driving PCa progression via caspase-1 activation. This study provides mechanistic insight into the NLRP3/caspase-1 axis and suggests it as a promising target for therapeutic intervention and clinical management of prostate cancer.
UR  - https://smerpub.com/article/activation-of-caspase-1-by-nlrp3-inflammasome-drives-malignant-progression-in-prostate-cancer-cp4wftxmrznuwuf
ER  -