Oleandrin Promotes Apoptosis in an Autophagy-Dependent Manner in Gastric Cancer
Xiaoyan Huang1,2, Liting Yan1,2, Xiangrong Zhao1,2
1Shaanxi Provincial Key Laboratory of Infection and Immune Diseases, Shaanxi Provincial People's Hospital, 710068 Xi'an, Shaanxi, China.
Background:
The medicinal phytochemical oleandrin (Ole) is obtained from the Nerium oleander plant. The exact relationship between Ole-induced apoptosis and autophagy in gastric cancer (GC) is unclear despite the fact that it has outstanding anti-tumor capabilities. This research aimed to demonstrate how autophagy and Ole-induced apoptosis interact in GC.
Methods:
The Cell Counting Kit (CCK)-8 assay and colony formation assays were employed to evaluate cell proliferation. Cellular apoptosis was evaluated with Calcein/Propidium Iodide (PI) assays and flow cytometry. Confocal and electron microscopes were employed to examine the morphology of autophagy. Protein concentrations were assessed by western blotting. Luciferase-positive HGC-27 cells were administered subcutaneously to Balb/c nude mice to evaluate Ole's anti-tumor activity. Immunohistochemistry assessed Ki67 expression and H&E staining in tumor tissue.
Results:
Ole causes GC cells to undergo intracellular apoptosis and autophagy at low nanomolar doses, halting the cell cycle at the G0/G1 phase. Whereas 3-methyladenine (3-MA), the inhibitor of autophagy, counteracts the apoptosis generated by Ole in vitro and in vivo.
Conclusions:
Ole may trigger apoptosis through the activation of autophagy in GC. It offers a secure and efficacious candidate drug for the treatment of tumors in the digestive system.
Insights
Ole, a phytochemical from Nerium oleander, triggers apoptosis and autophagy in gastric cancer (GC) cells. Autophagy activation by Ole may be key to its anti-cancer effects, suggesting its potential as a digestive system tumor treatment.
Area of Science:
- Pharmacology
- Cancer Biology
- Cellular Biology
Background:
- Oleandrin (Ole), a phytochemical from Nerium oleander, exhibits anti-tumor properties.
- The interplay between Ole-induced apoptosis and autophagy in gastric cancer (GC) remains incompletely understood.
- This study investigates the interaction between autophagy and Ole-induced apoptosis in GC.
Purpose of the Study:
- To elucidate the relationship between autophagy and apoptosis induced by oleandrin in gastric cancer.
- To evaluate the therapeutic potential of oleandrin in gastric cancer treatment.
Main Methods:
- Cell proliferation assessed using CCK-8 and colony formation assays.
- Apoptosis evaluated via Calcein/PI assays and flow cytometry.
- Autophagy morphology examined using confocal and electron microscopy; protein levels by western blotting; in vivo anti-tumor activity in mice.
Main Results:
- Ole induces apoptosis and autophagy in GC cells at low nanomolar concentrations, arresting the cell cycle at G0/G1.
- Autophagy inhibition using 3-methyladenine (3-MA) counteracted Ole-induced apoptosis both in vitro and in vivo.
- Ole demonstrated anti-tumor activity in a mouse model.
Conclusions:
- Ole may activate apoptosis via autophagy induction in gastric cancer.
- Ole shows promise as a safe and effective therapeutic candidate for digestive system tumors.
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