Emodin induces apoptosis in human promyeloleukemic HL-60 cells accompanied by activation of caspase 3 cascade but independent of reactive oxygen species production

Yen Chou Chen, Shing Chuan Shen, Woan Ruoh Lee, Foun Lin Hsu, Hui Yi Lin, Ching Huai Ko, Shi Wen Tseng

Research output: Contribution to journalArticle

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Abstract

Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is an active constituent of Rheum palmatum, and showed inhibitory activity on lipopolysaccharide-induced NO production in our previous study. However, the apoptosis-inducing activity of emodin has remained undefined. Among three structurally related anthraquinones, including emodin, physcion, and chrysophanol, emodin showed the most potent cytotoxic effects on HL-60 cells, accompanied by the dose- and time-dependent appearance of characteristics of apoptosis including an increase in DNA ladder intensity, morphological changes, appearance of apoptotic bodies, and an increase in hypodiploid cells. Emodin at apoptosis-inducing concentrations causes rapid and transient induction of caspase 3/CPP32 activity, but not caspase 1 activity, according to cleavage of caspase 3 substrates poly(ADP-ribose) polymerase and D4-GDI proteins, the appearance of cleaved caspase 3 fragments being detected in emodin- but not physcion- or chrysophanol-treated HL-60 cells. A decrease in the anti-apoptotic protein, Mcl-1, was detected in emodin-treated HL-60 cells, whereas other Bcl-2 family proteins including Bax, Bcl-2, Bcl-XL, and Bad remained unchanged. The caspase 3 inhibitor, Ac-DEVD-CHO, but not the caspase 1 inhibitor, Ac-YVAD-CHO, attenuated emodin-induced DNA ladders, associated with the blockage of PARP and D4-GDI cleavage. Free radical scavenging agents including NAC, catalase, SOD, ALL, DPI, L-NAME and PDTC showed no preventive effect on emodin-induced apoptotic responses, whereas NAC, CAT and PDTC prevented HL-60 cells from ROS (H2O2)-induced apoptosis through inhibition of caspase 3 cascades. Induction of catalase, but not SOD, activity was detected in emodin-treated HL-60 cells by in gel activity assays, and H2O2-induced intracellular peroxide level was significantly reduced by prior treatment of emodin in HL-60 cells. Our experiments provide evidence that emodin is an effective apoptosis inducer in HL-60 cells through activation of the caspase 3 cascade, but that it is independent of ROS production.

Original languageEnglish
Pages (from-to)1713-1724
Number of pages12
JournalBiochemical Pharmacology
Volume64
Issue number12
DOIs
Publication statusPublished - Dec 15 2002

Fingerprint

Emodin
HL-60 Cells
Caspase 3
Reactive Oxygen Species
Chemical activation
Apoptosis
Guanine Nucleotide Dissociation Inhibitors
Ladders
Catalase
Rheum
bcl-2-Associated X Protein
Caspase 1
Anthraquinones
Apoptosis Regulatory Proteins
Caspase Inhibitors
Poly(ADP-ribose) Polymerases
DNA
NG-Nitroarginine Methyl Ester
Scavenging
Peroxides

Keywords

  • Apoptosis
  • Caspase 3
  • Catalase
  • Emodin
  • ROS
  • SOD

ASJC Scopus subject areas

  • Pharmacology

Cite this

Emodin induces apoptosis in human promyeloleukemic HL-60 cells accompanied by activation of caspase 3 cascade but independent of reactive oxygen species production. / Chen, Yen Chou; Shen, Shing Chuan; Lee, Woan Ruoh; Hsu, Foun Lin; Lin, Hui Yi; Ko, Ching Huai; Tseng, Shi Wen.

In: Biochemical Pharmacology, Vol. 64, No. 12, 15.12.2002, p. 1713-1724.

Research output: Contribution to journalArticle

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