División de Inmunología, Centro de Investigación Biomédica de Occidente, IMSS, Guadalajara, Mexico.
Immunopharmacol Immunotoxicol. 2009 Jun;31(2):320-30. doi: 10.1080/08923970902718049.
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.
本研究旨在确定原花色素对健康供体血液中多形核白细胞和单核细胞活力和活性的影响。原花色素孵育后，人多形核白细胞和单核细胞的线粒体膜电位（Δψm）丧失和凋亡达到最大值。用半胱天冬酶-9 抑制剂或抗氧化剂（超氧化物歧化酶或 Trolox）预处理可抑制原花色素诱导的Δψm 丧失和凋亡。同样，我们观察到半胱天冬酶-3、-7 和-10 参与了原花色素诱导的凋亡。暴露于原花色素的多形核白细胞中促凋亡基因 bax、bak、bad 和 p53/Tp53 的表达增加。多形核白细胞和单核细胞用原花色素处理时，抗凋亡基因 bcl-(XL)和 mcl-1 的表达减少。原花色素处理还抑制了这些细胞对酵母的吞噬作用。我们得出结论，原花色素诱导吞噬细胞凋亡，且这种作用呈剂量依赖性。鉴于原花色素可能用于癌症治疗的临床策略，本报告中的发现可能很重要。
