Background Crocin, a natural plant extract, shows potential anti-inflammatory and anti-tumor effects. The research explore Crocin’s therapeutic potential in Prostate cancer (PCa) and mechanism of action, with the expectation of providing a novel candidate for PCa. Methods Crocin’s cytotoxicity on PCa was appraised with Cell counting kit-8 assay. Abilities of proliferation, migration, and invasion were assessed via 5-Ethynyl-2-Deoxyuridine (EdU) staining, colony formation, wound healing, and transwell assays. Apoptosis rate was detected by Flow Cytometry. The levels of proteins associated with Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) pathway and Nod-like receptor protein 3 (NLRP3) inflammasome were detected. Additionally, a tumor-bearing mouse model was used to evaluate Crocin’s anti-tumor effects in vivo. Results Crocin reduced the viability of PCa cells, particularly LnCaP and 22RV1. Under the action of Crocin, EdU positivity rate, colony formation number, wound healing rate, and number of invaded cells were significantly reduced, while apoptosis rate increased. Crocin downregulated TLR4, p-NF-κB p65, p-IκBα, and NLRP3, inhibiting TLR4/NF-κB pathway and NLRP3. This resulted in reducing secretion of pro-inflammatory cytokines. Crocin inhibited tumor growth in vivo, and the changes of TLR4/NF-κB pathway and NLRP3 related proteins levels were consistent with those in vitro. Conclusion Crocin inhibits PCa progression by blocking TLR4/NF-κB and NLRP3. This study provides a theoretical basis for the use of Crocin in the treatment of PCa. Graphical abstract Crocin could inhibit TLR4/NF-κB and NLRP3 activating, reducing inflammatory factors generating, thus inhibiting PCa proliferation, migration, and invasion and inducing apoptosis. Highlights <OrderedList> <ListItem> <ItemNumber>1.</ItemNumber> <ItemContent> Crocin can reduce PCa cells viability and induce cell damage and apoptosis. </ItemContent> </ListItem> <ListItem> <ItemNumber>2.</ItemNumber> <ItemContent> Crocin suppresses PCa growth and metastasis. </ItemContent> </ListItem> <ListItem> <ItemNumber>3.</ItemNumber> <ItemContent> Crocin inhibits PCa malignant progression by suppressing TLR4/NF-κB and NLRP3 from activing. </ItemContent> </ListItem> <ListItem> <ItemNumber>4.</ItemNumber> <ItemContent> Crocin can inhibit PCa tumor growth in vivo. </ItemContent> </ListItem> </OrderedList>

Crocin suppresses prostate cancer progression via TLR4/NF-κB and NLRP3 pathway inhibition

期刊论文
发表日期：

2025年12月10日

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Ankang Yu,
Mingqiang Li

摘要

Background

Crocin, a natural plant extract, shows potential anti-inflammatory and anti-tumor effects. The research explore Crocin’s therapeutic potential in Prostate cancer (PCa) and mechanism of action, with the expectation of providing a novel candidate for PCa.

Methods

Crocin’s cytotoxicity on PCa was appraised with Cell counting kit-8 assay. Abilities of proliferation, migration, and invasion were assessed via 5-Ethynyl-2-Deoxyuridine (EdU) staining, colony formation, wound healing, and transwell assays. Apoptosis rate was detected by Flow Cytometry. The levels of proteins associated with Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) pathway and Nod-like receptor protein 3 (NLRP3) inflammasome were detected. Additionally, a tumor-bearing mouse model was used to evaluate Crocin’s anti-tumor effects in vivo.

Results

Crocin reduced the viability of PCa cells, particularly LnCaP and 22RV1. Under the action of Crocin, EdU positivity rate, colony formation number, wound healing rate, and number of invaded cells were significantly reduced, while apoptosis rate increased. Crocin downregulated TLR4, p-NF-κB p65, p-IκBα, and NLRP3, inhibiting TLR4/NF-κB pathway and NLRP3. This resulted in reducing secretion of pro-inflammatory cytokines. Crocin inhibited tumor growth in vivo, and the changes of TLR4/NF-κB pathway and NLRP3 related proteins levels were consistent with those in vitro.

Conclusion

Crocin inhibits PCa progression by blocking TLR4/NF-κB and NLRP3. This study provides a theoretical basis for the use of Crocin in the treatment of PCa.

Graphical abstract

Crocin could inhibit TLR4/NF-κB and NLRP3 activating, reducing inflammatory factors generating, thus inhibiting PCa proliferation, migration, and invasion and inducing apoptosis.

Highlights

Crocin can reduce PCa cells viability and induce cell damage and apoptosis.

Crocin suppresses PCa growth and metastasis.

Crocin inhibits PCa malignant progression by suppressing TLR4/NF-κB and NLRP3 from activing.

Crocin can inhibit PCa tumor growth in vivo.