Ursolic acid (UA) has been reported to possess anticancer activities. Although 
some of the anticancer activities of UA have been explained by its 
apoptosis-inducing properties, the mechanisms underlying its anticancer actions 
are largely unknown. We have found that UA-activated autophagy induced 
cytotoxicity and reduced tumor growth of cervical cancer cells TC-1 in a 
concentration-dependent manner. UA did not induce apoptosis of TC-1 cells in 
vitro as determined by annexin V/propidium iodide staining, DNA fragmentation, 
and Western blot analysis of the apoptosis-related proteins. We found that UA 
increased punctate staining of light chain 3 (LC3), which is an autophagy 
marker. LC3II, the processed form of LC3I which is formed during the formation 
of double membranes, was induced by UA treatment. These results were further 
confirmed by transmission electron microscopy. Wortmannin, an inhibitor of 
autophagy, and a small interfering RNA (siRNA) for autophagy-related genes 
(Atg5) reduced LC3II and simultaneously increased the survival of TC-1 cells 
treated with UA. We also found that LC3II was significantly reduced and that 
survival was increased in Atg5-/- mouse embryonic fibroblast (MEF) cells 
compared to Atg5+/+ MEF cells under UA treatment. However, silencing BECN1 by 
siRNA affected neither the expression of LC3II nor the survival of TC-1 cells 
under UA treatment. These results suggest that autophagy is a major mechanism by 
which UA kills TC-1 cells. It is Atg5 rather than BECN1 that plays a crucial 
role in UA-induced autophagic cell death in TC-1 cells. The activation of 
autophagy by UA may become a potential cancer therapeutic strategy complementing 
the apoptosis-based therapies. Furthermore, regulation of Atg5 may improve the 
efficacy of UA in cancer treatment.