α-Hederin Induces Apoptosis of Esophageal Squamous Cell Carcinoma via an Oxidative and Mitochondrial-Dependent Pathway
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α-Hederin has been shown promising anti-tumor potential against various cancer cell lines. However, reports about effects of α-hederin on esophageal squamous cell carcinoma (ESCC) are still unavailable.
To investigate the inhibitory effects of α-hederin on ESCC and explore the underlying mechanism.
Human esophageal carcinoma cell line (Eca-109) was used for the experiment. Cell Counting Kit-8, flow cytometry, Hoechst 33258 staining, enhanced ATP assay kit, 2′,7′-dichlorofluorescin diacetate, JC-1 kit, and Western bolt were used to assess the cell viability, cycle, apoptosis, cellular ATP content, reactive oxygen species (ROS) level, mitochondrial membrane potential (MMP), and protein expression, respectively, in vitro. Xenografted tumor model was constructed to evaluate the in vivo anti-tumor effects of α-hederin.
Compared with control group, α-hederin significantly inhibited the proliferation, induced apoptosis of ESCC, and arrested the cell cycle in G1 phase (P < 0.05). α-Hederin induced the accumulation of ROS, decrement of ATP levels, and disruption of MMP (P < 0.05). The detection of mitochondrial and cytosol proteins showed that AIF, Apaf-1, and Cyt C were released and increased in cytoplasm, and then, caspase-3, caspase-9, and Bax were involved and increased, while Bcl-2 level was decreased (P < 0.05). Furthermore, the above changes were amplified in the group pretreated with l-buthionine sulfoximine, while N-acetyl-l-cysteine plays an opposite role (P < 0.05). Meanwhile, α-hederin significantly inhibited the growth of xenografted tumors with favorable safety.
α-Hederin could inhibit the proliferation and induce apoptosis of ESCC via dissipation of the MMP with simultaneous ROS generation and activation of the mitochondrial pathway.
Keywordsα-Hederin Esophageal squamous cell carcinoma Apoptosis Oxidative stress Mitochondria
This study is supported by the National Natural Science Foundation of China (No. 81572426), the Natural Science Foundation of Hubei Province (No. 2015CKB755) and the Youth Fund of Beijing Shijitan Hospital (No. 2016-q07).
Compliance with Ethical Standards
Conflict of interest
All authors declare that they have no conflict of interest.
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