Costunolide Induces Autophagy and Apoptosis by Activating ROS/MAPK Signaling Pathways in Renal Cell Carcinoma

Frontiers in Oncology
Dian FuZhenyu Xu

Abstract

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 exe...Continue Reading

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Citations

Jul 25, 2021·International Journal of Molecular Sciences·Hai HuangMyoung Ok Kim
Oct 1, 2021·BioFactors·Alfredo Cruz-GregorioMaría Elena Ibarra-Rubio

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Methods Mentioned

BETA
fluorescence microscopy
Assay
flow cytometry
PCR

Software Mentioned

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