Integrative approach to decipher pharmacological mechanism of Cinnamomum zeylanicum essential oil in prostate cancer

Abstract

Prostate cancer has garnered much importance in recent years due to its rising incidence and mortality among men worldwide. The ineffectiveness of existing therapies and adverse events associated with conventional treatment have led patients to turn towards traditional medicine for the management of prostate cancer. Cinnamomum zeylanicum bark essential oil (CZEO) possesses promising anticancer properties, yet the exact mechanism of action of CZEO for the management of prostate cancer remains unclear. Therefore, the current study tried to elucidate the bioactive components and key potential targets through which CZEO may exert its anticancer effect for treating prostate cancer. Fifty-nine constituents were identified by GC-MS, of which 52 were drug-like constituents. A total of 2847 targets related to CZEO and 2283 targets related to prostate cancer were obtained from public databases and the GEO dataset. Twenty-three overlapping targets exist between CZEO and disease targets. Compound-disease-target network analysis revealed camphor, eugenol, methyl eugenol, trans farnesyl acetate and nerol as the core bioactive ingredients of CZEO. The topological screening of the PPI network revealed BCL2, TNF, NFKBIA, CREBBP and IL7R as potential hub targets. These hub targets were validated based on mRNA expression level, pathological stages, overall survival, immune infiltrate and genetic alteration analysis in prostate adenocarcinoma and normal patients. KEGG enrichment analysis proposed that CZEO exhibits its anticancer effect mainly by modulating the PI3-AKT and MAPK signalling pathway. Moreover, molecular docking and dynamics simulation studies revealed a good binding affinity of these core compounds with TNF, NFKBIA and BCL2. CZEO exhibited a remarkable anti-proliferative effect against PC-3 cells with an IC₅₀ value of 13.56 µg/mL. CZEO promoted apoptosis and cell cycle arrest in the G2/M phase in PC-3 cells. CZEO-induced apoptosis was due to loss of mitochondrial membrane potential, increase in reactive oxygen species levels and activation of caspases (caspase 3, caspase 8 and caspase 9). RT-qPCR analysis revealed that CZEO modulated the mRNA expression level of hub genes (BCL2, TNF, NFKBIA, CREBBP, and IL7R, caspase 3, caspase 8 and caspase 9). The present study provides a mechanistic approach of Cinnamomum zeylanicum essential oil against prostate cancer.

Keywords: Essential oil; Multitarget effects; Natural compounds; Network pharmacology; Prostate cancer.