Extracts of Artocarpus communis Induce Mitochondria-Associated Apoptosis via Pro-oxidative Activity in Human Glioblastoma Cells

Frontiers in Pharmacology
Chiang-Wen LeeMing-Horng Tsai

Abstract

Glioblastoma multiforme (GBM) is an extremely aggressive and devastating malignant tumor in the central nervous system. Its incidence is increasing and the prognosis is poor. Artocarpin is a natural prenylated flavonoid with various anti-inflammatory and anti-tumor properties. Studies have shown that artocarpin is associated with cell death of primary glioblastoma cells. However, the in vivo effects and the cellular and molecular mechanisms modulating the anticancer activities of artocarpin remain unknown. In this study, we demonstrated that treating the glioblastoma cell lines U87 and U118 cells with artocarpin induced apoptosis. Artocarpin-induced apoptosis is associated with caspase activation and poly (ADP-ribose) polymerase (PARP) cleavage and is mediated by the mitochondrial pathway. This is associated with mitochondrial depolarization, mitochondrial-derived reactive oxidative species (ROS) production, cytochrome c release, Bad and Bax upregulations, and Bcl-2 downregulation. Artocarpin induced NADPH oxidase/ROS generation plays an important role in the mitochondrial pathway activation. Furthermore, we found artocarpin-induced ROS production in mitochondria is associated with Akt- and ERK1/2 activation. After treatment wi...Continue Reading

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Citations

Jan 31, 2019·Biomolecules·Xiao-Long YuanZhong-Feng Zhang
Dec 13, 2019·Bioscience, Biotechnology, and Biochemistry·Hua JiangJingming Yang
May 3, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Mariana MagalhãesCélia Cabral

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Methods Mentioned

BETA
surgical resection
Xenograft
enzyme-linked immunosorbent assay
protein assay
flow cytometry
Assay
xenografts
PCR

Software Mentioned

GraphPad Prism

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