The relationship between polyamines and apoptosis is still not well defined. Various cell lines respond differently to polyamine depletion. Yuan et al.29 reported that polyamine depletion prevented apoptosis of rat intestinal epithelial cells by decreasing caspase 3 and 9 activities, as well as the translocation of Bax to mitochondria, thus diminishing cytochrome c release. Similarly, Landau et al.30 showed that polyamine depletion in NIH3T3 cells led to cell cycle arrest but not apoptosis. In contrast, most reports demonstrated that polyamine depletion induced apoptosis in tumor cells.31, 32 The mitochondrial pathway is a primary pathway of apoptosis involving Bcl-2 family members, cytochrome c release and activation of caspase 3.33 Wildtype p53 is a tumor suppressor gene that plays a key role in DNA damage repair. But when DNA damage is beyond repair, p53 induces Bax expression, which guides cells into apoptosis.34 The homodimerization of Bcl-2 leads to anti-apoptosis signaling and Bax can heterodimerize with Bcl-2 to induce apoptosis.35 Moreover, Bax has been reported to induce cytochrome c release that in turn activates caspase 3.36 Poly ADP ribose polymerase (PARP) is an important enzyme that plays a key role in DNA repair and apoptosis.37 Once PARP has been cleaved by caspases, apoptosis is induced.38 In the present study, polyamine depletion by shODC enhanced the expression of p53, increasing the expression level of Bax. Then caspase 3 was activated and cleaved PARP, inducing apoptosis (Fig. 3). At the same time, the expression of Bcl-2 was decreased. Our results confirmed that inhibiting polyamine synthesis in ESCC cells resulted in cell death due to apoptosis.