Objective       To assay the role of terpinen-4-ol in inducing autophagy and inhibiting proliferation in human lung adenocarcinoma A549 cells in vitro and explore its possible mechanism related to autophagy pathway.       Methods       A549 cells were incubated with various concentrations of terpinen-4-ol. MTT assay was used to observe the inhibitory effect of terpinen-4-ol on the growth of A549 cells and determine its IC

50

. The changes of

cell cycle

apoptosis and intracellular free calcium concentration were measured by flow cytometry. The ultrastructure of A549 cells were observed by transmission electron microscopy before and after terpinen-4-ol treatment. After xenograft transplantation tumor of A549 cells (1×10

6

with the diameter over 0.5 cm) were established in nude mice

terpinen-4-ol was injected  intra-peritoneally for 10 d and then the   nude mice were killed. Transplantation tumor were taken and then detected. Real-time fluorescent quantitative PCR and Western blotting were performed to detect the expression of BECN1 and LC3 in the A549 cells and the transplantation tumor.       Results       MTT assay showed that the viability of A549 cells was in a dose-dependent manner after the cells were treated with terpinen-4-ol for 24 h

with a IC

50

value of 0.067%. The cell cycle was arrested in S phase according to the results of flow cytometry

and cell apoptosis was induced by terpinen-4-ol and the intracellular calcium concentrations were significantly higher in treatment groups than the control group (P0.05). Transmission electron microscopy displayed that there were more autophagic vacuoles in the A594 cells treated by terpinen-4-ol. Low and high-dose treatment resulted in the growth of the transplantation tumor obviously restrained (tumor inhibitory rate of 53.33% and 77.76% respectively). Real-time PCR and Western blot analysis showed that terpinen-4-ol inhibited the mRNA and protein levels of BECN1 and LC3 (P0.05).       Conclusion       Terpinen-4-ol induces autophagy and inhibits cell proliferation in A549 cells in vitro and in vivo．