Cyclin D1 is an inhibitor of cell cycle and promotes progression from G1 to S. Its expression is elevated in tumor cells, and it is relevant with abnormal proliferation, invasion, and prognosis of tumor cells (Alao 2007). Conversely, P21 and p27 are implicated in the negative regulation of cell cycle progression from G1 to S phase by modulating the activity of CDKs (Lu and Hunter 2010). It is reported that AKT could positively regulate cyclin D1 expression and negatively regu- late the expression of p21 and p27 (Manning and Cantley 2007; Liang et al. 2002). Therefore, in this study, we can draw that lupeol induced cell cycle arrest at G1 phase by decreasing cyclin D1 and increasing p21 and p27 through inactivation of AKT.