CN-3 induces mitochondrial apoptosis in glioma via Ros-mediated PI3K/AKT pathway.

Abstract

Recently we isolated CN-3, a new asterosaponin from starfish Culcita novaeguineae, and reported that asterosaponin arrests glioma cell cycle via SCUBE3. However, the multiple mechanisms underlying CN-3 anti-glioma action remains poorly known. Thus, the focus of this study was to evaluate the inhibitory effect of CN-3 on human glioma cells and its underlying molecular mechanisms. U87 and U251 cells were incubated with various concentrations of CN-3, and CCK-8, transmission electron microscopy, ICELLigence, TUNEL, flow cytometry, N-acetyl-<small>L</small>-cysteine, and western blot were conducted. As a result, it was found that CN-3 significantly inhibited U87 and U251 cell viability and proliferation in a time- and dose- dependent manner, and also induced mitochondrial apoptosis. Furthermore, we detected that CN-3 downregulated PI3K, P-Akt, AKT and BCL-2, and upregulated cytochrome C and BAX in U87 and U251 cells. Moreover, ROS triggered the inhibition and cell apoptosis for CN-3 via inactivation of P-Akt and activation of cytochrome C. In conclusion, these findings suggest that CN-3 may be a promising candidate for the development of a therapy of glioma.

• Authors: Yu-Ye Xue, Yun-Yang Lu, Guang-Qiang Sun, Fei Fang, Yu-Qiang Ji, Hai-Feng Tang, Peng-Cheng Qiu, Guang Cheng
• Journal: Die Pharmazie (Pharmazie) Vol. 76 Issue 5 Pg. 208-214 (05 01 2021) ISSN: 0031-7144 [Print] Germany
• PMID: 33964994 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apoptosis Regulatory Proteins
• Calcium-Binding Proteins
• Reactive Oxygen Species
• SCUBE3 protein, human
• Saponins
• Cytochromes c
• Proto-Oncogene Proteins c-akt
• Sincalide

Topics

• Animals
• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins (metabolism)
• Calcium-Binding Proteins (metabolism)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Cytochromes c (metabolism)
• Glioma (drug therapy)
• Humans
• Mitochondria (drug effects)
• Phosphatidylinositol 3-Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Reactive Oxygen Species (metabolism)
• Saponins (chemistry, pharmacology)
• Signal Transduction (drug effects)
• Sincalide (pharmacology)
• Starfish (chemistry)