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

Biochem Pharmacol. 2002 Dec 15;64(12):1713-24. doi: 10.1016/s0006-2952(02)01386-2.


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 (H(2)O(2))-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 H(2)O(2)-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Caspase 1 / metabolism
  • Caspase 3
  • Caspase Inhibitors
  • Caspases / metabolism*
  • Catalase / metabolism
  • Cysteine Proteinase Inhibitors / pharmacology
  • Drug Interactions
  • Emodin / pharmacology*
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology*
  • Free Radical Scavengers / pharmacology
  • Guanine Nucleotide Dissociation Inhibitors / metabolism
  • HL-60 Cells
  • Humans
  • Leukemia, Myeloid / pathology*
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Neoplasm Proteins / metabolism
  • Oligopeptides / pharmacology
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases
  • Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2*
  • Reactive Oxygen Species / metabolism*
  • Superoxide Dismutase / metabolism
  • rho Guanine Nucleotide Dissociation Inhibitor beta
  • rho-Specific Guanine Nucleotide Dissociation Inhibitors


  • ARHGDIB protein, human
  • Caspase Inhibitors
  • Cysteine Proteinase Inhibitors
  • Enzyme Inhibitors
  • Free Radical Scavengers
  • Guanine Nucleotide Dissociation Inhibitors
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Neoplasm Proteins
  • Oligopeptides
  • Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • acetyl-aspartyl-glutamyl-valyl-aspartal
  • rho Guanine Nucleotide Dissociation Inhibitor beta
  • rho-Specific Guanine Nucleotide Dissociation Inhibitors
  • Catalase
  • Superoxide Dismutase
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases
  • CASP3 protein, human
  • Caspase 3
  • Caspases
  • Caspase 1
  • Emodin