Involvement of reactive oxygen species-independent mitochondrial pathway in gossypol-induced apoptosis

De-Xing Hou; Takuhiro Uto; Xuhui Tong; Toru Takeshita; Shunsuke Tanigawa; Izumi Imamura; Takashi Ose; Makoto Fujii

doi:10.1016/j.abb.2004.06.007

Involvement of reactive oxygen species-independent mitochondrial pathway in gossypol-induced apoptosis

Arch Biochem Biophys. 2004 Aug 15;428(2):179-87. doi: 10.1016/j.abb.2004.06.007.

Authors

De-Xing Hou¹, Takuhiro Uto, Xuhui Tong, Toru Takeshita, Shunsuke Tanigawa, Izumi Imamura, Takashi Ose, Makoto Fujii

Affiliation

¹ Department of Biochemical Science and Technology, Faculty of Agriculture, Kagoshima University, Korimoto 1-21-24, Kagoshima 890-0065, Japan. [email protected]

PMID: 15246875
DOI: 10.1016/j.abb.2004.06.007

Abstract

Gossypol is a component present in cottonseeds and has been demonstrated to be an effective contraceptive drug in preventing spermatogenesis in mammalian species. In the present, we reported that gossypol could induce apoptosis in human promyelocytic leukemia cells (HL-60), as characterized by DNA fragmentation, poly(ADP) ribose polymerase (PARP) cleavage. The efficacious induction of apoptosis was observed at 50 microM for 6 h. Further molecular analysis showed that gossypol induced the truncation of Bid protein, the loss of mitochondrial membrane potential (DeltaPsi m), cytochrome c release from mitochondria into cytosol, and activation of caspase-3, -8, and -9. However, gossypol did not increase the level of reactive oxygen species (ROS), and antioxidants including N-acetyl cysteine (NAC) and catalase could not block gossypol-induced apoptosis in the HL-60 cells. These data suggest that gossypol induces apoptosis in HL-60 cells through ROS-independent mitochondrial dysfunction pathway.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetylcysteine / metabolism
Apoptosis*
BH3 Interacting Domain Death Agonist Protein
Blotting, Western
Carrier Proteins / metabolism
Caspase 3
Caspase 8
Caspase 9
Caspases / metabolism
Catalase / metabolism
Cell Survival
Contraceptive Agents, Male / pharmacology
Cytochromes c / metabolism
Cytosol / metabolism
DNA Fragmentation
Dose-Response Relationship, Drug
Electrophoresis, Agar Gel
Flow Cytometry
Gossypol / pharmacology*
HL-60 Cells
Humans
Membrane Potentials
Mitochondria / metabolism
Mitochondria / pathology*
Poly(ADP-ribose) Polymerases / metabolism
Reactive Oxygen Species*
Subcellular Fractions
Time Factors

Substances

BH3 Interacting Domain Death Agonist Protein
BID protein, human
Carrier Proteins
Contraceptive Agents, Male
Reactive Oxygen Species
Cytochromes c
Catalase
Poly(ADP-ribose) Polymerases
CASP3 protein, human
CASP8 protein, human
CASP9 protein, human
Caspase 3
Caspase 8
Caspase 9
Caspases
Gossypol
Acetylcysteine