α‐Hederin induces the apoptosis of gastric cancer cells accompanied by glutathione decrement and reactive oxygen species generation via activating mitochondrial dependent pathway

Abstract

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.

Dual Role of Reactive Oxygen Species and their Application in Cancer Therapy

“…Then, Cyt c interacts with apoptotic protease activating factor 1 to form an apoptosome, leading to caspase-9 and caspase-3 activation and subsequent cell apoptosis 123 . The administration of α-hederin can induce the overexpression of ROS and activate the mitochondrial apoptotic pathway, finally triggering the apoptosis of gastric cancer cells 95 . Similarly, in vitro studies have found that metal thiourea complexes can work as a new antitumor metallodrug to kill HeLa cells via a burst of the ROS-regulated mitochondria apoptotic pathway 114 .…”

“…However, the massive accumulation of ROS plays an antioncogenic role in cancer. Extensive accumulation of ROS can inhibit tumor cell proliferation [93] and lead to cancer cell death, which can be explained by the activation of ER stress-, mitochondrial-, P53-apoptotic pathways and the ferroptosis pathway in cancer [94][95][96] (Fig. 4, Fig.…”

Disulfiram Chelated with Copper Promotes Apoptosis in Osteosarcoma <i>via</i> ROS/Mitochondria Pathway

“…As an early event in the process of apoptosis, GSH depletion will promote the occurrence of apoptosis. 18) A study has shown that the apoptosis of gastric cancer accompanied by glutathione decrement via activating mitochondrial dependent pathway. 19) There are some studies which have also shown that intracellular GSH levels are associated with drug resistance in a variety of tumors, 18,[20][21][22] such as leukemia, colon cancer, lung cancer and so on.…”

“…18) A study has shown that the apoptosis of gastric cancer accompanied by glutathione decrement via activating mitochondrial dependent pathway. 19) There are some studies which have also shown that intracellular GSH levels are associated with drug resistance in a variety of tumors, 18,[20][21][22] such as leukemia, colon cancer, lung cancer and so on. However, reducing the GSH levels in tumor cells by taking some measures can significantly increase the sensitivity of tumor cells to chemotherapeutic drugs and improve the effect of tumor chemotherapies.…”

Selective anticancer effects of Serjania marginata Casar. extract in gastric cells are mediated by antioxidant response

“…alternative for the treatment of gastric cancer. 6,7 In Brazil, the population often use medicinal plants as alternative therapies, 8 including several species of the Serjania genus for the treatment of stomach pain, inflammation, and ulcer. 9,10 Serjania marginata Casar.…”