Abstract

We investigate the roles of methoxyl (OCH3) 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 OCH3 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 IC50 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-diOCH3, 7,8-diOCH3, and 7-OCH3-8-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.

Original languageEnglish
Pages (from-to)1394-1404
Number of pages11
JournalJournal of Cellular Biochemistry
Volume103
Issue number5
DOIs
Publication statusPublished - Apr 1 2008

Fingerprint

Hydroxyl Radical
Leukemia
HL-60 Cells
Flavonoids
Apoptosis
Assays
Peroxides
Ladders
Caspase 3
Flavones
norwogonin
wogonin
DNA
Structure-Activity Relationship
Cytotoxicity
Processing
Catalase
Inhibitory Concentration 50
Proteins
Substitution reactions

Keywords

  • Apoptosis
  • Nor-wogonin
  • Structure-activity relationship
  • Wogonin

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

@article{b6ea86cda256438094f5e00a5787eaf0,
title = "Differential apoptotic effect of wogonin and nor-wogonin via stimulation of ROS production in human leukemia cells",
abstract = "We investigate the roles of methoxyl (OCH3) 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 OCH3 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 IC50 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-diOCH3, 7,8-diOCH3, and 7-OCH3-8-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.",
keywords = "Apoptosis, Nor-wogonin, Structure-activity relationship, Wogonin",
author = "Jyh-Ming Chow and Huang, {Guan Cheng} and Shing-Chuan Shen and Wu, {Chin Yen} and Cheng-Wei Lin and Yen-Chou Chen",
year = "2008",
month = "4",
day = "1",
doi = "10.1002/jcb.21528",
language = "English",
volume = "103",
pages = "1394--1404",
journal = "Journal of Cellular Biochemistry",
issn = "0730-2312",
publisher = "Wiley-Liss Inc.",
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TY - JOUR

T1 - Differential apoptotic effect of wogonin and nor-wogonin via stimulation of ROS production in human leukemia cells

AU - Chow, Jyh-Ming

AU - Huang, Guan Cheng

AU - Shen, Shing-Chuan

AU - Wu, Chin Yen

AU - Lin, Cheng-Wei

AU - Chen, Yen-Chou

PY - 2008/4/1

Y1 - 2008/4/1

N2 - We investigate the roles of methoxyl (OCH3) 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 OCH3 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 IC50 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-diOCH3, 7,8-diOCH3, and 7-OCH3-8-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.

AB - We investigate the roles of methoxyl (OCH3) 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 OCH3 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 IC50 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-diOCH3, 7,8-diOCH3, and 7-OCH3-8-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.

KW - Apoptosis

KW - Nor-wogonin

KW - Structure-activity relationship

KW - Wogonin

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U2 - 10.1002/jcb.21528

DO - 10.1002/jcb.21528

M3 - Article

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SP - 1394

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JO - Journal of Cellular Biochemistry

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SN - 0730-2312

IS - 5

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