Polyphenols from Korean prostrate spurge Euphorbia supina induce apoptosis through the Fas-associated extrinsic pathway
and activation of ERK in human leukemic U937 cells

Han,Min-Ho; Lee,Won  Sup; Nagappan,Arulkumar; Kim,Hye  Jung; Park,Cheol; Kim,Gi-Young; Hong,Sang  Hoon; Kim,Nam  Deuk; Kim,Gonsup; Ryu,Chung  Ho; Shin,Sung  Chul; Choi,Yung  Hyun

doi:10.3892/or.2016.4778

Polyphenols from Korean prostrate spurge Euphorbia supina induce apoptosis through the Fas-associated extrinsic pathway and activation of ERK in human leukemic U937 cells

Authors:
- Min-Ho Han
- Won Sup Lee
- Arulkumar Nagappan
- Hye Jung Kim
- Cheol Park
- Gi-Young Kim
- Sang Hoon Hong
- Nam Deuk Kim
- Gonsup Kim
- Chung Ho Ryu
- Sung Chul Shin
- Yung Hyun Choi
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Affiliations: Natural Products Research Team, National Marine Biodiversity Institute of Korea, Seocheon 325-902, Republic of Korea, Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Republic of Korea, Department of Pharmacology, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Republic of Korea, Department of Molecular Biology, College of Natural Sciences and Human Ecology, Dongeui University, Busan 614-714, Republic of Korea, Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Republic of Korea, Department of Internal Medicine, Dongeui University College of Korean Medicine, Busan 614-052, Republic of Korea, Department of Pharmacy, College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea, School of Veterinary Medicine, Research Institute of Life Science, Gyeongsang National University, Jinju 660-701, Republic of Korea, Division of Applied Life Science (BK 21 Program), Research Institute of Life Science, Gyeongsang National University, Jinju 660-701, Republic of Korea, Department of Chemistry, Research Institute of Life Science, Gyeongsang National University, Jinju 660-701, Republic of Korea, Department of Biochemistry, Dongeui University College of Korean Medicine, Busan 614-052, Republic of Korea
Published online on: April 28, 2016 https://doi.org/10.3892/or.2016.4778
Pages: 99-107
Copyright: © Han et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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