Xu K, Thornalley P J
Department of Biological Sciences, University of Essex, Central Campus, Wivenhoe Park, Colchester, Essex, CO4 3SQ, UK.
Br J Cancer. 2001 Mar 2;84(5):670-3. doi: 10.1054/bjoc.2000.1636.
Phenethyl isothiocyanate and allyl isothiocyanate induce apoptosis of human leukaemia HL60 cells in vitro. Apoptosis was associated with cleavage of p22 BID protein to p15, p13 and p11 fragments and activation of JNK and tyrosine phosphorylation (18 kDa and 45 kDa proteins). All these effects and apoptosis were prevented by exogenous glutathione (15 mM). Protein tyrosine phosphatase activity was unchanged. The general caspase inhibitor Z-VAD-fmk prevented apoptosis but not JNK activation - excluding a role for caspases in JNK activation, whereas curcumin prevented JNK activation but only delayed apoptosis. This suggests that in isothiocyanate-induced apoptosis, the caspase pathway has an essential role, the JNK pathway a supporting role, and inhibition of protein tyrosine phosphatases is not involved.
苯乙基异硫氰酸酯和烯丙基异硫氰酸酯在体外诱导人白血病HL60细胞凋亡。凋亡与p22 BID蛋白裂解为p15、p13和p11片段以及JNK激活和酪氨酸磷酸化（18 kDa和45 kDa蛋白）有关。所有这些效应和凋亡都被外源性谷胱甘肽（15 mM）所阻止。蛋白质酪氨酸磷酸酶活性未改变。通用的半胱天冬酶抑制剂Z-VAD-fmk可阻止凋亡，但不能阻止JNK激活——排除了半胱天冬酶在JNK激活中的作用，而姜黄素可阻止JNK激活，但仅延迟凋亡。这表明在异硫氰酸酯诱导的凋亡中，半胱天冬酶途径起关键作用，JNK途径起辅助作用，且不涉及蛋白质酪氨酸磷酸酶抑制。
