Iodinin (1,6-dihydroxyphenazine 5,10-dioxide) from Streptosporangium sp. induces apoptosis selectively in myeloid leukemia cell lines and patient cells.
Iodinin (1,6-dihydroxyphenazine 5,10-dioxide) from Streptosporangium sp. induces apoptosis selectively in myeloid leukemia cell lines and patient cells.
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DOI：
10.3390/md11020332
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发表时间：
2013-01-30
期刊：
影响因子：
5.4
通讯作者：
Herfindal L
中科院分区：
文献类型：
--
作者：
Myhren LE;Nygaard G;Gausdal G;Sletta H;Teigen K;Degnes KF;Zahlsen K;Brunsvik A;Bruserud Ø;Døskeland SO;Selheim F;Herfindal L
尽管最近在治疗方面有所改进，但急性髓系白血病(AML)仍然与高致死率有关。在目前的研究中，我们分析了来自海洋放线菌细菌的生物活性化合物碘(1，6-二羟基吩嗪5，10-二氧化物)在一系列细胞类型中诱导细胞死亡的能力。Iodinin对急性髓系白血病和急性早幼粒细胞白血病细胞表现出选择性毒性，白血病细胞的EC50值比正常细胞低40倍。Iodinin还成功地诱导了患者来源的白血病细胞或细胞系的细胞死亡，这些细胞系具有与不良预后相关的特征，如Flt3内部串联复制或突变/缺失的p53。细胞死亡具有典型的凋亡形态，并激活了caspase-3等凋亡信号蛋白。分子模拟表明，碘可以以类似于抗癌药物柔红霉素(DNR)的方式嵌入DNA中的碱基之间，导致DNA链断裂。Iodinin诱导了几种耐药AML患者原始细胞的凋亡，但对外周血白细胞的诱导程度较低，与DNR相反，对大鼠心肌母细胞不诱导凋亡。对通常受抗白血病治疗影响的正常细胞类型的低活性表明，碘及其相关化合物在抗癌治疗的发展中具有很好的结构。
Despite recent improvement in therapy, acute myeloid leukemia (AML) is still associated with high lethality. In the presented study, we analyzed the bioactive compound iodinin (1,6-dihydroxyphenazine 5,10-dioxide) from a marine actinomycetes bacterium for the ability to induce cell death in a range of cell types. Iodinin showed selective toxicity to AML and acute promyelocytic (APL) leukemia cells, with EC50 values for cell death up to 40 times lower for leukemia cells when compared with normal cells. Iodinin also successfully induced cell death in patient-derived leukemia cells or cell lines with features associated with poor prognostic such as FLT3 internal tandem duplications or mutated/deficient p53. The cell death had typical apoptotic morphology, and activation of apoptotic signaling proteins like caspase-3. Molecular modeling suggested that iodinin could intercalate between bases in the DNA in a way similar to the anti-cancer drug daunorubicin (DNR), causing DNA-strand breaks. Iodinin induced apoptosis in several therapy-resistant AML-patient blasts, but to a low degree in peripheral blood leukocytes, and in contrast to DNR, not in rat cardiomyoblasts. The low activity towards normal cell types that are usually affected by anti-leukemia therapy suggests that iodinin and related compounds represent promising structures in the development of anti-cancer therapy.
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影响因子：
3.1
作者：
de Koning, Barbara A. E.;Lindenbergh-Kortleve, Dicky J.;Pieters, Rob;Buller, Hans A.;Renes, Ingrid B.;Einerhand, Alexandra W. C.
通讯作者：
Einerhand, Alexandra W. C.
影响因子：
4.8
作者：
Dai, JX;Punchihewa, C;Yang, DZ
通讯作者：
Yang, DZ
影响因子：
5.8
作者：
Gavasso, S.;Gjertsen, B. T.;Vedeler, C.
通讯作者：
Vedeler, C.
LEDGF/p75的表达增加了抗化疗的人类急性髓性白血病患者的爆炸表达，并保护白血病细胞不受体外凋亡。
影响因子：
37.3
作者：
Huang, Tien-sheng;Myklebust, Line M;Kjarland, Endre;Gjertsen, Bjorn Tore;Pendino, Frederic;Bruserud, Oystein;Doskeland, Stein Ove;Lillehaug, Johan R
通讯作者：
Lillehaug, Johan R
影响因子：
12.4
作者：
Krakstad, C.;Herfindal, L.;Doskeland, S. O.
通讯作者：
Doskeland, S. O.