Induction of HL60 cell differentiation by tiazofurin and its analogues: characterization and efficacy.

Induction of HL60 cell differentiation by tiazofurin and its analogues: characterization and efficacy.
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DOI:
10.1182/blood.v78.3.593.593
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发表时间:
1991-08
期刊:
影响因子:
20.3
通讯作者:
B. Goldstein;J. Leary;B. Farley;V. Marquez;P. C. Levy;P. Rowley
B. Goldstein;J. Leary;B. Farley;V. Marquez;P. C. Levy;P. Rowley
中科院分区:
医学1区
文献类型:
--
作者:
B. Goldstein;J. Leary;B. Farley;V. Marquez;P. C. Levy;P. Rowley

文献摘要

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在白血病细胞的髓系分化诱导剂中,噻唑呋喃因其作用机制已知而特别受关注;它抑制肌苷单磷酸脱氢酶,从而减少鸟嘌呤核苷酸池。本文从三个方面介绍了噻唑呋喃诱导HL60人急性早幼粒细胞白血病细胞向髓系分化的作用。首先,评价了化合物Ara-tiazofurin、xylo-tiazofurin和seenazofurin,二核苷酸同源代谢物TAD和SAD,以及抗磷酸二酯酶的TAD类似物β-亚甲基TAD的诱导效果。结果表明,母体化合物是比二核苷酸衍生物更有效的诱导剂,硒唑类似物是比噻唑类化合物更有效的诱导剂。其次,噻唑呋喃与抗病毒药物利巴韦林对HL60细胞的诱导有协同作用。最后发现,噻唑呋喃能诱导HL60细胞上磷脂酰肌醇特异性磷脂酶C敏感的Fcγ受体III(FcRIII)的表达,这一特征与中性粒细胞分化一致,但不是单核细胞分化。
Among inducers of myeloid differentiation for leukemic cells, tiazofurin is of special interest because its mechanism of action is known; it inhibits inosine monophosphate dehydrogenase and thus decreases the guanine nucleotide pool. Reported here are three aspects of tiazofurin induction of myeloid differentiation in HL60 human acute promyelocytic leukemia cells. First, inductive efficacy was evaluated for analogues ara-tiazofurin, xylo-tiazofurin, and selenazofurin, for dinucleotide anabolites thiazole-4-carboxamide adenine dinucleotide (TAD) and selenazole-4-carboxamide adenine dinucleotide (SAD), and for a phosphodiesterase-resistant TAD analogue, beta-methylene TAD. The results showed that the parent compounds are more effective inducers than the dinucleotide derivatives and that the selenazole analogues are more effective inducers than the thiazole compounds. Second, HL60 cell induction by tiazofurin was shown to be synergistic with that produced by the antiviral agent ribavirin. Finally, tiazofurin was found to induce expression of a phosphatidylinositol-specific phospholipase C-sensitive Fc gamma-receptor III (FcRIII) on HL60 cells, a feature consistent with neutrophilic, but not monocytic, differentiation.