Differential apoptotic effect of wogonin and nor-wogonin via stimulation of ROS production in human leukemia cells

✍ Scribed by Jyh-Ming Chow; Guan-Cheng Huang; Shing-Chuan Shen; Chin-Yen Wu; Cheng-Wei Lin; Yen-Chou Chen

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 463 KB
• Volume: 103
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.21528

✦ Synopsis

Abstract

We investigate the roles of methoxyl (OCH~3~) and hydroxyl (OH) substitutions at C8 of flavonoids on their apoptosis‐inducing activities. Wogonin (Wog) and nor‐wogonin (N‐Wog) are structurally related flavonoids, and respectively contain an OH and OCH~3~ at C8. In leukemia HL‐60 cells, N‐Wog exhibited more‐potent cytotoxicity than Wog according to the MTT and LDH release assays, and the IC~50~ values of Wog and N‐Wog in HL‐60 cells were 67.5 ± 2.1 and 21.7 ± 1.5 µM, respectively. Apoptotic characteristics including DNA ladders, apoptotic bodies, and hypodiploid cells accompanied by the induction of caspase 3 protein processing appeared in Wog‐ and N‐Wog‐treated HL‐60 cells. Interestingly, an increase in intracellular peroxide production was detected in N‐Wog‐ but not Wog‐treated HL‐60 cells by the DCHF‐DA assay, and the reduction of intracellular peroxide by catalase (CAT) induced by N‐Wog significantly reduced the N‐Wog‐ but not the Wog‐induced cytotoxic effect according to the MTT assay in accordance with the blocking of DNA ladder formation and caspase 3 and PARP protein processing elicited by N‐Wog. We further analyzed the effect of six structurally related compounds, including 5‐OH, 7‐OH, 5,7‐diOH, 5,7‐diOCH~3~, 7,8‐diOCH~3~, and 7‐OCH~3~‐8‐OH flavones, on apoptosis induction in HL‐60 cells. Results suggested that OH at C5 and C7 is essential for both the apoptosis‐inducing activity of flavonoids, and OH at C8 may contribute to apoptosis induction ability. Evidence to support a distinct structure‐activity relationship in apoptosis induction of flavonoids is provided for the first time in this study. J. Cell. Biochem. 103: 1394–1404, 2008. © 2007 Wiley‐Liss, Inc.