1. Polyphenols from Korean prostrate spurge Euphorbia supina induce apoptosis through the Fas-associated extrinsic pathway and activation of ERK in human leukemic U937 cells.
- Author
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Han MH, Lee WS, Nagappan A, Kim HJ, Park C, Kim GY, Hong SH, Kim ND, Kim G, Ryu CH, Shin SC, and Choi YH
- Subjects
- Antineoplastic Agents isolation & purification, BH3 Interacting Domain Death Agonist Protein metabolism, Baculoviral IAP Repeat-Containing 3 Protein, Caspase 3 metabolism, Caspase 8 metabolism, Caspase 9 metabolism, Cell Line, Tumor, Cell Proliferation drug effects, Cytochromes c metabolism, DNA Fragmentation drug effects, Enzyme Activation drug effects, G1 Phase Cell Cycle Checkpoints drug effects, Humans, Inhibitor of Apoptosis Proteins metabolism, Leukemia pathology, MAP Kinase Signaling System drug effects, Membrane Potential, Mitochondrial drug effects, Phosphoinositide-3 Kinase Inhibitors, Poly(ADP-ribose) Polymerases metabolism, Polyphenols isolation & purification, Republic of Korea, U937 Cells, Ubiquitin-Protein Ligases metabolism, X-Linked Inhibitor of Apoptosis Protein metabolism, bcl-2-Associated X Protein biosynthesis, bcl-Associated Death Protein biosynthesis, Antineoplastic Agents pharmacology, Apoptosis drug effects, Euphorbia chemistry, Extracellular Signal-Regulated MAP Kinases metabolism, Leukemia drug therapy, Phytochemicals pharmacology, Polyphenols pharmacology
- Abstract
The Korean prostrate spurge Euphorbia supina (Euphorbiaceae family) has been used as a folk medicine in Korea against a variety of ailments such as bronchitis, hemorrhage, jaundice and multiple gastrointestinal diseases. Polyphenols from Korean E. supina (PES) which include quercetin and kaempferol derivatives have anticancer properties. Hence, we investigated the anticancer effects of PES on U937 human leukemic cells. Firstly, PES significantly inhibited the proliferation of U937 cells in a dose-dependent manner. PES induced accumulation of the sub-G1 DNA content (apoptotic cell population), apoptotic bodies and chromatin condensation and DNA fragmentation in the U937 cells. PES also induced activation of caspase-3, -8 and -9, subsequent cleavage of PARP, and significantly suppressed XIAP, cIAP-1 and cIAP-2 in a dose-dependent manner. Furthermore, PES activated Bid, and induced the loss of mitochondrial membrane potential (MMP, ΔΨm) along with upregulation of pro-apoptotic proteins (Bax and Bad), and downregulation of anti-apoptotic proteins (Bcl-2 and Bcl-xL) and cytochrome c release. The Fas receptor was upregulated by PES in a dose-dependent manner, suggesting that the extrinsic pathway was also involved in the PES-induced apoptosis. Moreover, the PES-induced apoptosis was at least in part associated with extracellular signal-regulated kinase (ERK) activation in the U937 human leukemic cells. This study provides evidence that PES may be useful in the treatment of leukemia.
- Published
- 2016
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