Paeonol upregulates expression of tumor suppressors TNNC1 and SCARA5, exerting anti-tumor activity in non-small cell lung cancer cells.

Paeonol, a naturally bioactive phenolic ingredient predominantly isolated from Paeonia suffruticosa, has recently garnered significant interest as an anti-tumor agent against diverse carcinomas including non-small cell lung cancer (NSCLC). However, the anti-tumor mechanism of paeonol in NSCLC remains unclear. Cell viability, caspase-3 activity, and apoptosis were evaluated using CCK-8 assay, Caspase-3 Colorimetric Assay Kit, and flow cytometry analysis, respectively. GSE186218 was downloaded from NCBI Gene Expression Omnibus (GEO). The common genes were screened using GEO2R and Draw Venn Diagram software. Expression of troponin C type 1 (TNNC1), scavenger receptor class A member 5 (SCARA5), phosphorylated protein kinase B (AKT) (p-AKT) and AKT was examined using GEPIA database, qRT-PCR and western blot analysis. Paeonol treatment concentration-dependently inhibited cell viability and increased caspase-3 activity and apoptotic rate in NSCLC cells. Only 5 overlapping genes including TNNC1 and SCARA5 were obtained among 232 upregulated genes in GSE186218, 200 underexpressed genes in TCGA-LUAD, and 200 underexpressed genes in TCGA-LUSC according to the Venn diagram software. TNNC1 and SCARA5, two known tumor suppressors, were significantly downregulated in LUAD and LUSC tissues and NSCLC cells. Paeonol dose-dependently upregulated TNNC1 and SCARA5 expression in NSCLC cells. Paeonol suppressed the AKT pathway by upregulating TNNC1 and SCARA5 expression. AKT inhibitor attenuated the effects of TNNC1 or SCARA5 knockdown on the anti-tumor activity of paeonol. In conclusion, paeonol exhibited anti-cancer activity in NSCLC cells through inactivating the AKT pathway by upregulating TNNC1 or SCARA5.