PLA inhibits TNF-α-induced PANoptosis of prostate cancer cells through metabolic reprogramming.

Previous studies have shown that phenyllactic acid (alpha-Hydroxyhydrocinnamic acid, 2-Hydroxy-3-phenylpropionic acid, PLA), a type of organic acid metabolite, has excellent diagnostic efficacy when used to differentiate between prostate cancer, benign prostatic hyperplasia, and prostatitis. This research aims to explore the molecular mechanism by which PLA influences the PANoptosis of prostate cancer (PCa) cell lines. First, we found that PLA was detected in all prostate cancer cell lines (PC-3, PC-3 M, DU145, LNCAP). Further experiments showed that the addition of PLA to prostate cancer cells could promote ATP generation, enhance cysteine desulfurase (NFS1) expression, and reduce tumor necrosis factor alpha (TNF-α) levels, thereby inhibiting apoptosis in prostate cancer cells. Notably, overexpression of NFS1 can inhibit the binding of TNF-α to serpin mRNA binding protein 1 (SERBP1), suggesting that NFS1 competes with TNF-α for binding to SERBP1. Knockdown of SERBP1 significantly reduced the level of small ubiquity-related modifier (SUMO) modification of TNF-α. This suggests that NFS1 reduces the SUMO modification of TNF-α by competing with SERBP1, thereby reducing the expression and stability of TNF-α and ultimately inhibiting apoptosis in prostate cancer cell lines. In conclusion, PLA inhibits TNF-α induced panapoptosis of prostate cancer cells through metabolic reprogramming, providing a new idea for targeted treatment of prostate cancer.

Network pharmacology and bioinformatics were used to construct a prognostic model and immunoassay of core target genes in the combination of quercetin and kaempferol in the treatment of colorectal cancer.

Purpose: CRC is a malignant tumor seriously threatening human health. Quercetin and kaempferol are representative components of traditional Chinese medicine (TCM). Previous studies have shown that both quercetin and kaempferol have antitumor pharmacological effects, nevertheless, the underlying mechanism of action remains unclear. To explore the synergy and mechanism of quercetin and kaempferol in colorectal cancer. Methods: In this study, network pharmacology, and bioinformatics are used to obtain the intersection of drug targets and disease genes. Training gene sets were acquired from the TCGA database, acquired prognostic-related genes by univariate Cox, multivariate Cox, and Lasso-Cox regression models, and validated in the GEO dataset. We also made predictions of the immune function of the samples and used molecular docking to map a model for binding two components to prognostic genes. Results: Through Lasso-Cox regression analysis, we obtained three models of drug target genes. This model predicts the combined role of quercetin and kaempferol in the treatment and prognosis of CRC. Prognostic genes are correlated with immune checkpoints and immune infiltration and play an adjuvant role in the immunotherapy of CRC. Conclusion: Core genes are regulated by quercetin and kaempferol to improve the patient's immune system and thus assist in the treatment of CRC.