Gossypol induced apoptosis of polymorphonuclear leukocytes and monocytes: involvement of mitochondrial pathway and reactive oxygen species.
The aim of this study was to determine how gossypol affects the viability and activity of polymorphonuclear leukocytes and monocytes in blood obtained from healthy donors. Loss of mitochondrial membrane potential (delta psi m) and apoptosis was maximized in human polymorphonuclear leukocytes and monocytes after incubation with gossypol. Pretreatment with a caspase-9 inhibitor or antioxidants (superoxide dismutase or Trolox) inhibited gossypol-induced loss of the delta psi m and apoptosis. Likewise, we observed participation of caspase -3, -7, and -10 in gossypol-induced apoptosis. Expression of the proapoptotic genes bax, bak, bad and p53/Tp53 increased in polymorphonuclear leukocytes exposed to gossypol. The expression of the anti-apoptotic genes bcl-(XL) and mcl-1 was reduced when polymorphonuclear leukocytes and monocytes were treated with gossypol. Gossypol treatment also inhibited yeast phagocytosis by these cells. We concluded that gossypol induces apoptosis in phagocytic cells and that this effect was dose-dependent. The findings in this report may be important to consider in light of possible gossypol use in clinical strategies for cancer treatment.
Barba-Barajas
Martha
M
División de Inmunología, Centro de Investigación Biomédica de Occidente, IMSS, Guadalajara, Mexico.
Hernández-Flores
Georgina
G
Lerma-Díaz
José M
JM
Ortiz-Lazareno
Pablo C
PC
Domínguez-Rodríguez
Jorge R
JR
Barba-Barajas
Leticia
L
de Celis
Ruth
R
Jave-Suarez
Luis F
LF
Aguilar-Lemarroy
Adriana C
AC
Guevara-Barraza
Mario G
MG
Bravo-Cuellar
Alejandro
A
D000328:Adult; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D002839:Chromans / Q000378:metabolism; D019938:Cyclin D1 / Q000096:biosynthesis; D005260:Female; D006072:Gossypol / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects*; D009000:Monocytes / Q000187:drug effects*; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009504:Neutrophils / Q000187:drug effects*; D010587:Phagocytosis / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D055815:Young Adult; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000096:biosynthesis; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis; D051025:bcl-Associated Death Protein / Q000096:biosynthesis
D000975:Antioxidants; D002839:Chromans; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D019938:Cyclin D1; D013482:Superoxide Dismutase; D020169:Caspases; D006072:Gossypol; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid