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

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 microM, 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.
AuthorsJyh-Ming Chow, Guan-Cheng Huang, Shing-Chuan Shen, Chin-Yen Wu, Cheng-Wei Lin, Yen-Chou Chen
JournalJournal of cellular biochemistry (J Cell Biochem) Vol. 103 Issue 5 Pg. 1394-404 (Apr 1 2008) ISSN: 1097-4644 [Electronic] United States
PMID17955493 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright2007 Wiley-Liss, Inc.
Chemical References
  • Flavanones
  • Flavones
  • Flavonoids
  • Reactive Oxygen Species
  • norwogonin
  • wogonin
  • CASP3 protein, human
  • Caspase 3
  • Apoptosis (drug effects)
  • Caspase 3 (metabolism)
  • DNA Fragmentation (drug effects)
  • Flavanones (chemistry, pharmacology)
  • Flavones
  • Flavonoids (chemistry, pharmacology)
  • HL-60 Cells
  • Humans
  • Leukemia (metabolism)
  • Reactive Oxygen Species (metabolism)
  • Structure-Activity Relationship

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: