Table 2 Proinflammatory cytokines (interleukins) and CXC chemokine-targeted strategies in preclinical and clinical studies in PCa
Anticancer drugs/inhibitors | Target | Type of study | Outcome/result |
|---|---|---|---|
Antagonist (IL-1RN) | CXCL1 and CXCL10 | Preclinical | CXCL1 and CXCL10 are inhibited by the secret IL-1RN produced by recruited TILs [239] |
Tumor-infiltrating leukocytes (TILs)/CD11b− | CXCL1 | Preclinical | TILs/CD11b cells protect androgen-dependent cells against CXCL1 damage [260] |
Lipocalin-2 (LCN2) knockout | IL-1β | Preclinical | LCN2 deficiency leads to reduced IL-1β [261] |
Arbutin | IL-1β | Preclinical | Arbutin could significantly decrease IL-1β [262] |
Germacranolides 1 and 2 | IL-1β and IL-8 | Preclinical | Germacranolides 1 and 2 reduce IL-1β and IL-8 [249] |
Rye whole grain and bran products | TNF-R2 | Clinical | The RP diet lowered the expression of TNF-R2 [263] |
Gnetum gnemon | IL-2 | Clinical | Reduce IL-2 [264] |
Panax notoginseng | IL-4 | Preclinical | Reduces IL-4 [265] |
Resolvin D1 and D2 | IL-4 and IFN-γ | Preclinical | RvD1 and RvD2 both inhibit LPS-IFNγ- and promote IL-4 [266] |
Androgen deprivation therapy | IL-6 and IL-10 | Preclinical | IL-10 and IL-6 were significantly lower in ADT-sensitive patients [246] |
Nexrutine and exercise | IL-1β, IL-5, IL-12, and VEGF | Clinical | Both interventions reduced the concentrations of the mentioned cytokines[267] |
Euterpe oleracea fruit | IL-6 | Preclinical | Reduced IL-6 and induce IFN-γ [268] |
GuBen-ZengGu granules | IL-6 and TNF-α | Clinical | Reduce the serum levels of IL-6 and TNF-α [269] |
Docetaxel plus degarelix | IL-6 and IL-10 | Clinical | Docetaxel plus degarelix reduce levels of IL-6 and IL-10 [270] |
Mangiferin functionalized gold nanoparticulate | IL-6 and IL-10 | Preclinical | MGF-AuNPs enhance IL-10 and IL-6 [271] |
IL-15 and ADU-S100 | PCa cells | Preclinical | IL-15 and ADU-S100 analogs induce the activation of NK cells and the resulting death of PCa cells [242, 272] |
Cyto-IL-15 | IL-15 | Preclinical | Cyto-IL-15 leads to PCa growth delay [273] |
6-Shogaol from dried ginger | IL-6- And TNF-α | Clinical/preclinical | 6-SHO reduced IL-6 and TNF-α [274] |
AgNPs of Annona muricata | CXCL1/CXCR2 | Preclinical | AgNPs help to downregulate the CXCL1/CXCR2 axis [275] |
Fucoxanthin | CXCL5, TGF-β, IL6, MMP1, TIMP1, and TIMP2 | Preclinical | Fuco downregulated the expressions of the mentioned genes [276] |
Walterinnesia aegyptia venom (WEV) + silica nanoparticles | CXCL9/10/12/13/16 CXCR3/4/5/6 | Preclinical | WEV + NP decrease the mentioned CXCLs and their receptors [248] |
Andrographolide | CXCL11/CXCR3/7 | Preclinical | AG inhibits PCa CXCL11/CXCR3/7 by targeting cell cycle regulators [277] |
chloroform | VEGF-A and CXCL-12 | Preclinical | MPc inhibit VEGF-A and CXCL-12 [278] |
MiR-206 | CXCL11 | In vivo | CXCL11-targeting MiR-206 suppresses PCa cell growth and migration [202] |
Agaricus bisporus (white button mushroom) | IL-8 and VEGF | Preclinical | IL-8 and VEGF suppression by mushrooms may affect tumor growth [279] |
Enzalutamide | IL-6 and STAT3 axis | Preclinical | Inhibition of IL-6 and STAT3 axis [250] |
IL-12 expressing NV1042 oncolytic herpes simplex virus | IL-2 | Clinical/preclinical | Effective method to improve antitumor efficiency in the treatment of PCa [237, 238] |
Recombinant IFN-α | IFN-α | Clinical | Administered IFN-α straight into the prostate. A phase I trial found that recombinant IFN-α had a positive impact [240] |
IFN-α-2b combined with docetaxel | IFN-α | Clinical | A low dose of IFN-α2b may enhance docetaxel’s anticancer properties [241] |
Diosmetin | IL-6 | Preclinical | Diosmetin inhibited IL-6 and IGF-1-induced PKC/Akt phosphorylation. Diosmetin may change Akt and PKCα phosphorylation, inhibiting PCa cell growth and viability [280] |
Chimeric antigen receptor (CAR) T-cell therapy | IL-7 | Preclinical | In xenograft models, natural killer group 2D ligand-targeting CAR T cells with IL-7 gene alteration showed improved antitumor effectiveness and longer overall survival (OS) [252] |
E966-0530-45418 | TGF-β | Preclinical | E966-0530-45418 reduces PCa metastasis by inhibiting CDK8 activity, TGF-β1-mediated Smad3/RNA polymerase II linker phosphorylation, and Akt/GSK3β/β-catenin signaling [281] |
ZY-444 | TNF signaling | Preclinical | ZY-444 targets TNFAIP3 via TNF signaling to decrease PCa growth and metastasis [282] |
Receptor antagonist IL-1RA | IL-1α and IL-1β | Clinical | IL-1RA may prevent IL-1α and IL-1β activity in PCa [283] |
CXCR2 blockade | TNF-α | Preclinical | CXCR2 re-educates macrophages, releases TNF-α, induces senescence, and inhibits PCa development [284] |
Endothelial cell-specific molecule-1 (ESM-1) knockdown | CXCL3 | Preclinical | ESM-1 inhibition decreased movement and expression of the angiogenic CXCL3 in PC-3 cells [285] |
CRISPR/Cas9-mediated deletion of IL30 | CXCL5 | Preclinical | IL-30 deletion greatly lowers CXCL5 expression in PCa cells [286] |
FAK (PF-573228) or MAPKK (PD98059) | CXCL6, IL-6, and CXCL5 | Preclinical | Mesenchymal stem cells (MSC) proinflammatory cytokines/chemokine phenotypes induced by IL-1 were suppressed by FAK and MAPKK inhibitors [287] |