Potent apoptosis-inducing activity of erypoegin K, an isoflavone isolated from Erythrina poeppigiana, against human leukemia HL-60 cells
- 213 Downloads
Erypoegin K is an isoflavone isolated from the stem bark of Erythrina poeppigiana. It contains a furan group at the A-ring of the core isoflavone structure and can inhibit the activity of glyoxalase I, an enzyme that catalyzes the detoxification of methylglyoxal (MG), a by-product of glycolysis. In the present study, we found that erypoegin K has a potent cytotoxic effect on human leukemia HL-60 cells. Its cytotoxic effect was much stronger than that of a known glyoxalase I inhibitor S-p-bromobenzylglutathione cyclopentyl diester. Conversely, erypoegin K demonstrated weak cytotoxicity toward normal human peripheral lymphocytes. The treatment of HL-60 cells with erypoegin K significantly induced caspase-3 activity, whereas the pretreatment of the cells with caspase-3 inhibitor suppressed erypoegin K-induced cell death. Furthermore, nuclear condensation and apoptotic genome DNA fragmentation were observed in erypoegin K-treated HL-60 cells. These results indicated that the observed cell death was mediated by apoptosis. In addition, the toxic compound MG was highly accumulated in the culture medium of erypoegin K-treated HL-60 cells, suggesting that cell apoptosis was triggered by extracellular MG. The present study showed that erypoegin K has a potent apoptosis-inducing effect on cancerous cell lines, such as HL-60.
KeywordsErythrina poeppigiana Erypoegin K Apoptosis Glyoxalase I Methylglyoxal HL-60 cells
This work was partly supported by a Grant-in-Aid for Scientific Research (C) (JP16K08311) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
Compliance with ethical standards
Conflict of interest
The authors declare no conflicts of interest.
- 4.Tanaka H, Etoh H, Kulkarni A, Fukai T (2004) Phenolic constituents and alkaloids from Erythrina species. Recent Res Devel Phytochem 8:83–116Google Scholar
- 5.Tanaka H, Oh-Uchi T, Nitanda T, Baba M, Etoh H, Shimizu H (2002) Prenylated cinnamylphenols, HIV-1 replication inhibitors, from Erythrina poeppigiana. Ite Lett Batter New Technol Med 3:612–615Google Scholar
- 8.Hikita K, Yamada S, Shibata R, Katoh M, Murata T, Kato K, Tanaka H, Kaneda N (2015) Inhibitory Effect of isoflavones from Erythrina poeppigiana on the growth of HL-60 human leukemia cells through inhibition of glyoxalase I. Nat Prod Commun 10:1581–1584Google Scholar
- 13.Racker E (1951) The mechanism of action of glyoxalase. J Biol Chem 190:685–696Google Scholar
- 14.Warburg O (1956) On respiratory impairment in cancer cells. Science 124:269–270Google Scholar
- 17.Sakamoto H, Mashima T, Sato S, Hashimoto Y, Yamori T, Tsuruo T (2001) Selective activation of apoptosis program by S-p-bromobenzylglutathione cyclopentyl diester in glyoxalase I-overexpressing human lung cancer cells. Clin Cancer Res 7:2513–2518Google Scholar
- 21.Sakamoto H, Mashima T, Kizaki A, Dan S, Hashimoto Y, Naito M, Tsuruo T (2000) Glyoxalase I is involved in resistance of human leukemia cells to antitumor agent-induced apoptosis. Blood 95:3214–3218Google Scholar
- 33.Boyum A (1968) Isolation of mononuclear cells and granulocytes from human blood. Scand J Clin Lab Invest Suppl 97:77–89Google Scholar