Esophageal cancer is of high prevalence and poor prognosis.
Hesperetin has been reported to exert antitumor ability by inducing apoptosis in many
cancers in vitro and in vivo without obvious toxicity. However, there is no study concerning about the effect of
hesperetin on
esophageal cancer. In this study, we aimed to investigate whether
hesperetin could induce apoptosis in
esophageal cancer cells and explore its potential mechanism. We found that
hesperetin induced
esophageal cancer cells apoptosis in a concentration-dependent and time-dependent manner compared with the untreated cells.
Hoechst 33258 staining and flow cytometry analysis showed more apoptotic cells in the
hesperetin-treated group (p < 0.05, respectively). The intracellular
reactive oxygen species (ROS) increased significantly, and
glutathione (GSH) was depleted. The loss of △Ψ m was more tremendous in the
hesperetin-treated cells.
N-acetylcysteine (NAC) reduced the proapoptotic ability of
hesperetin, while DL-
buthionine-S, R-sulfoximine (BSO) enhanced the anticancer effect. Western blotting showed that the expression levels of
cytochrome C (Cyt C) and
apoptosis-inducing factor (AIF) decreased in mitochondria and increased in cytoplasm (p < 0.05). The levels of intracellular cleaved
caspase-9, cleaved
caspase-3, Apaf-1,
Bcl-2-associated X protein (Bax), and suppressor of fused (SuFu) increased, while
B cell lymphoma 2 (Bcl-2) and
Survivin decreased. What is more, in xenograft
tumor model,
hesperetin inhibited the
tumor growth significantly via induction of cell apoptosis which was detected by TUNEL assay (p < 0.05). Taken together, our study demonstrated that
hesperetin could induce cell apoptosis in
esophageal cancer cells via mitochondrial-mediated intrinsic pathway by accumulation of ROS.