Zanthoxylum bungeanum Seed Oil Elicits Autophagy and Apoptosis in Human Laryngeal Tumor Cells via PI3K/AKT/mTOR Signaling Pathway
Background: Zanthoxylum bungeanum seed oil (ZBSO) is a main extract of the edible drug Zanthoxylum bungeanum seeds. Recently reports proved that it has a significant cytotoxic effect on various cancer cells. However, systematic investigation on the roles of ZBSO in laryngeal carcinoma (LC) is rare. Objective: To reveal the function of ZBSO on human laryngeal squamous carcinoma cells (Hep-2) and to elucidate its underlying mechanism. Methods: In this study, the chemical composition analysis of ZBSO was done using Ultra Performance Liquid Chromatography (UPLC), and the anti-tumor effect of ZBSO on Hep-2 cells was evaluated by cell proliferation, apoptosis and cell cycle experiments. qRT-PCR, immunohistochemistry (IHC) and Western blotting were used for mechanistic investigation at the molecular level. Results: The main compound of ZBSO was identified as polyunsaturated fatty acids. Furthermore, as compared with normal cells, significant inhibitory activities of ZBSO was observed on Hep-2 cells with dose- and time-dependency, which induced apoptosis, blocked cell cycle at the S phase, and inhibited cell proliferation. In addition, IHC results showed difference in the level of protein expression of ZBSO-induced autophagy-related markers. At last, Western blotting results indicated that ZBSO could inhibit the expression and phosphorylation levels of PI3K/AKT/mTOR protein. Conclusions: The anti-LC effect of ZBSO might be intimately associated with the induction of autophagy and the inhibition of PI3K/AKT/mTOR signaling pathway. ZBSO may be a potential anti-laryngocarcinoma agent.