Gallic acid attenuates the malignant phenotype of prostate cancer cells by antagonizing NF-κB/KLF7/L1CAM expression

Prostate cancer (PCa) is a common malignancy of the urinary tract. Hormone therapy is the primary clinical option for the treatment of PCa; however, some PCa patients succumb to the disease due to malignant progression. This study aimed to identify new therapeutic agents for PCa and their potential molecular mechanisms of action, which will provide new insights into the treatment and prognosis of PCa.

Following the overexpression or knockdown of Krüppel-like factor 7 ( KLF7 ) in PC-3 cells, we performed RNA sequencing (RNA-seq) and bioinformatics analyses to identify oncogenic factors regulated by KLF7 . A dual-luciferase reporter assay, Chromatin immunoprecipitation (ChIP) and quantitative real-time polymerase chain reaction (qRT-PCR) were used to evaluate the transcriptional regulation of L1 cell adhesion molecule ( L1CAM ) by KLF7 Pca cells. The impact of NF-κB p65 phosphorylation (NF-κB p-p65) on KLF7 and L1CAM expression was investigated by qRT-PCR, Western blotting, and gallic acid (GA) treatment was applied to examine its effects on the proliferation, invasion, and migration of PC-3 cells by cell counting kit-8 (CCK8) assay, cell invasion and migration assays, cell scratch assay and colony formation assay. The binding affinity of GA for the NF-κB p65 protein was subsequently assessed via surface plasmon resonance (SPR) analysis. In vivo experiments were conducted using C57BL/6 mice models to evaluate the therapeutic potential of GA.

Our results demonstrated that high expression of KLF7 promoted the proliferation, invasion, and migration of PCa cells through the transcriptional activation of L1CAM . Additionally, phosphorylation of NF-κB p65 enhanced the malignant phenotype of PCa cells via upregulation of KLF7/L1CAM axis. GA attenuated the malignant phenotype of PCa cells by inhibiting the transcriptional activation of KLF7 via p-p65. Furthermore, in mice, GA gavage attenuated the malignant phenotype of PCa cells through the inhibition of p65.

These findings indicated that GA could decrease L1CAM expression by inhibiting the transcriptional activation of KLF7 via p-p65, in turn attenuating the malignant phenotype and tumorigenic capacity of PCa cells in vivo .