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Dioscin Induces Gallbladder Cancer Apoptosis by Inhibiting ROS-Mediated PI3K/AKT Signalling
Xiaoling Song1,2, Zheng Wang1,2, Haibin Liang1,2
1Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
Abstract:
Gallbladder cancer (GBC), highly aggressive form of cancer with an extremely poor prognosis, is the most common malignancy of the biliary tract. In this study, we investigated the effects of dioscin (DSN) on human GBC and the potential mechanisms underlying these effects. The results showed that DSN significantly inhibited GBC cell proliferation and migration. Moreover, DSN induced GBC cell apoptosis via mitochondrial dependent apoptotic signalling. Reactive oxygen species (ROS) and glutathione (GSH) levels were measured, and ROS scavengers completely inhibited DSN-induced apoptosis and migration, indicating that ROS play an essential role in GBC progression. Western blot analysis showed that AKT activity was significantly downregulated after DSN treatment, and that inhibition/ectopic expression of AKT enhanced/abolished DSN-induced apoptosis but not migration. Furthermore, we confirmed the relationship between ROS and the PI3K/AKT pathway and found that DSN induced apoptosis by regulating ROS-mediated PI3K/AKT signaling. Taken together, these findings indicate that DSN induces GBC apoptosis through inhibiting ROS-mediated PI3K/AKT signalling.
Insights
Dioscin (DSN) inhibits gallbladder cancer (GBC) cell growth and migration by inducing apoptosis. This natural compound targets reactive oxygen species (ROS) and the PI3K/AKT pathway, offering a potential therapeutic strategy for GBC.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Gallbladder cancer (GBC) is a highly aggressive malignancy with a poor prognosis.
- The biliary tract's most common cancer, GBC, necessitates novel therapeutic strategies.
- Understanding the molecular mechanisms of GBC progression is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the anti-cancer effects of dioscin (DSN) on human GBC cells.
- To elucidate the underlying molecular mechanisms of DSN's action in GBC.
- To explore the role of reactive oxygen species (ROS) and the PI3K/AKT pathway in DSN-mediated GBC apoptosis.
Main Methods:
- Cell proliferation and migration assays were performed.
- Apoptosis was assessed via mitochondrial-dependent signaling pathways.
- Western blot analysis was used to evaluate AKT activity.
- Reactive oxygen species (ROS) and glutathione (GSH) levels were measured.
Main Results:
- DSN significantly inhibited GBC cell proliferation and migration.
- DSN induced GBC cell apoptosis through mitochondrial-dependent signaling.
- ROS are essential for GBC progression, as ROS scavengers blocked DSN's effects.
- DSN downregulated AKT activity, and AKT modulation affected DSN-induced apoptosis.
Conclusions:
- DSN exhibits potent anti-cancer effects against human GBC cells.
- DSN induces apoptosis by regulating ROS-mediated PI3K/AKT signaling.
- These findings suggest DSN as a potential therapeutic agent for gallbladder cancer.
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