beta-hederin and Stomach-Neoplasms

α-Hederin, a monodesmosidic triterpenoid saponin, exhibited promising antitumor potential against a variety of human cancer cell lines. However, few related studies about effects of α-hederin on gastric cancer are available. Herein, our results showed that α-hederin significantly inhibited the proliferation of gastric cancer cells and arrested the cell cycle in G1 phase in vitro (p < .05). Further research of the potential mechanism reflected that α-hederin could induce intracellular glutathione decrement, adenosine triphosphate level, and mitochondrial membrane potential variation via inducing reactive oxygen species accumulation during the apoptosis of gastric cancer cells. Moreover, the detection of mitochondrial and cytosol proteins with apoptosis-inducing factor, apoptosis protease activating factor-1, and cytochrome C showed an increase in the cytosol, followed by a decrease of Bcl-2 levels and increases of caspase-3, caspase-8, caspase-9, and Bax, which revealed that α-hederin induced apoptosis via triggering activation of the mitochondrial pathway. Furthermore, the above changes were amplified when pretreated with buthionine sulfoximine, whereas attenuated in the group pretreated with NAC than α-hederin alone (p < .05). In addition, α-hederin significantly inhibited the growth of xenografted gastric tumors with favorable safety. In conclusion, α-hederin could inhibit the proliferation and induce apoptosis of gastric cancer accompanied by glutathione decrement and reactive oxygen species generation via activating mitochondrial dependent pathway.

Topics: Apoptosis; bcl-2-Associated X Protein; Caspases; Cell Line, Tumor; Cell Proliferation; Cytochromes c; Glutathione; Humans; Membrane Potential, Mitochondrial; Mitochondria; Oleanolic Acid; Proto-Oncogene Proteins c-bcl-2; Reactive Oxygen Species; Saponins; Stomach Neoplasms

Cisplatin is a type of broad-spectrum anti-carcinogen that has been widely used in anti-gastric cancer therapy. Drug resistance prevails in gastric cancer therapy. α-Hederin has been reported to exert anti-tumour ability by inducing apoptosis in many cancers in vitro and in vivo. A combination chemotherapy regimen can improve the outcome of patients.. In the present study, we used a CCK-8 assay, Hoechst 33258 staining, Annexin V-PE/7-AAD, intracellular reactive oxygen species (ROS) measurement, mitochondrial membrane potential (MMP) assay kit and western blotting to detect apoptosis and mitochondrial function in gastric cancer (GC) cells. A xenograft tumour model in nude mice was used to evaluate the anti-tumour effects of cisplatin and α-Hederin in vivo.. Combination treatment of cisplatin and α-Hederin increased the apoptotic effects in cisplatin-induced GC cell lines. In the xenograft mouse model, the combination of cisplatin and α-Hederin remarkably increased the tumour inhibition effect compared to either drug alone. Interestingly, combination of cisplatin and α-Hederin increased the expression of apoptosis-related proteins. Using in vitro experiments, we verified that the combination of cisplatin and α-Hederin increased the accumulation of ROS in GC cell lines and also reduced the MMP, thus inhibiting proliferation and promoting apoptosis in GC cells.. α-Hederin enhances cisplatin-induced anti-tumour effects in GC both in vitro and in vivo by promoting the accumulation of ROS and decreasing MMP. Our data strongly suggested that α-Hederin is a promising candidate for intervention in gastric cancer.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Apoptosis Regulatory Proteins; Cell Line, Tumor; Cell Proliferation; Cisplatin; Humans; Membrane Potential, Mitochondrial; Mice; Mice, Inbred BALB C; Mice, Nude; Mitochondria; Oleanolic Acid; Reactive Oxygen Species; Saponins; Signal Transduction; Stomach Neoplasms