Investigating the anti-osteosarcoma effects of Patchouli alcohol through protein network mapping and in vitro experiments

Abstract

Osteosarcoma is one of the most common malignant tumors in orthopedics, especially in the metaphysis of tubular bones of the extremities in adolescents. Patchouli alcohol (PA) is a tricyclic sesquiterpene isolated from Patchouli, a Labiatae family, which has been shown to have antitumor efficacy against a variety of cancers. However, the effects and mechanisms of PA against osteosarcoma remain to be elucidated. Sixty-three possible therapeutic targets of PA against osteosarcoma were identified by protein network mapping analysis. PPI network analysis and KEGG functional enrichment analysis showed that PA exerts significant therapeutic effects on osteosarcoma through multiple targets and pathways, especially the PI3K/Akt pathway. Molecular docking results indicated that PA had significant binding to EGFR, HSP90AA1, ESR1 and SRC targets. In vitro experiments, PA inhibited proliferation and induced G2/M arrest in osteosarcoma cells in a dose- and time-dependent manner. PA induced apoptosis in osteosarcoma cells through a decrease in mitochondrial membrane potential. Alterations in the expression of apoptosis-related proteins Bcl-2 and Bax also confirmed that PA promoted apoptosis in osteosarcoma cells. Treatment with PA promoted more autophagosome formation, increased autophagy-related protein LC3-II/I ratio as well as decreased p62 expression in osteosarcoma cells. In addition, PA decreased the expression of p-PI3K/PI3K, and p-Akt/Akt in osteosarcoma cells. These findings indicated that PA exerts anti-osteosarcoma effects by inhibiting osteosarcoma cell proliferation, inducing apoptosis, promoting autophagy and inhibiting PI3K/Akt pathway, suggesting PA as a potential agent against osteosarcoma.