Costunolide Induces Autophagy and Apoptosis by Activating ROS/MAPK Signaling Pathways in Renal Cell Carcinoma
| Autor: | Wen Cheng, Jianping Gao, Zhenyu Xu, Wen-Quan Zhou, Dian Fu, Zhengyu Zhang, Jing-Ping Ge, Ding Wu |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research Poly ADP ribose polymerase renal cancer ROS – reactive oxygen species Matrix metalloproteinase lcsh:RC254-282 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation costunolide Original Research Costunolide Cell growth Autophagy apoptosis lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens autophage Cell biology 030104 developmental biology Oncology chemistry Apoptosis Cytoplasm 030220 oncology & carcinogenesis |
| Zdroj: | Frontiers in Oncology, Vol 10 (2020) Frontiers in Oncology |
| ISSN: | 2234-943X |
| Popis: | Although costunolide (Cos), a natural sesquiterpene compound isolated from various medicinal plants, exhibits antiproliferative and pro-apoptotic effects in diverse types of cancers, the mechanism associated with the anticancer property of Cos has not been elucidated. The present investigation was carried out to study the anticarcinogenic influence of Cos on kidney cancer cells. Several human renal cancer cell lines were used and biological and molecular studies were conducted. It was found that Cos significantly suppressed renal carcinoma cell growth via stimulation of apoptosis and autophagy in a concentration-dependent manner. Further studies revealed that Cos increased Bax/Bcl-2 ratio, decreased mitochondrial transmembrane potential (MMP), and enhanced cytoplasmic levels of cytochrome c, and activation of caspase-9, caspase-3, and cleaved PARP, resulting in cell apoptosis. The autophagy induced by Cos resulted from the formation of GFP-LC3 puncta and upregulation of LC3B II and Beclin-1 proteins. Compared with Cos treatment, the autophagy inhibitor 3-MA or ROS scavenger NAC significantly inhibited apoptosis and autophagy. Moreover, NAC and JNK-specific inhibitor SP600125 attenuated the effect of Cos. Taken together, Cos exerted autophagic and apoptotic effects on renal cancer through the ROS/JNK-dependent signal route. These findings suggest that Cos could be a beneficial anticarcinogenic agent. |
| Databáze: | OpenAIRE |
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