Prevention of chemotherapy-induced alopecia by the anti-death FNK protein
Prevention of chemotherapy-induced alopecia by the anti-death FNK protein
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DOI：
10.1016/j.lfs.2007.11.011
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发表时间：
2008-01-16
期刊：
影响因子：
6.1
通讯作者：
Ohta, Shigeo
中科院分区：
文献类型：
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作者：
Nakashima-Kamimura, Naomi;Nishimaki, Kiyomi;Ohta, Shigeo
许多抗癌药物攻击快速分裂的细胞，不仅包括癌细胞，还包括毛囊细胞，并导致脱发。化疗诱导脱发(CIA)是癌症化疗的一种令人痛苦的副作用。目前还没有对CIA有效的预防性治疗方法。我们先前已经从大鼠(L)的Bclx中通过定点突变构建了抗死亡的rFNK蛋白，以增强细胞保护活性。融合蛋白PTD(TAT)-rFNK与HIV/TAT的蛋白转导结构域(PTD)融合后，在体外和体内均能成功进入细胞，表现出抗细胞凋亡和抗坏死的活性。在这里，我们展示了局部应用FNK在新生大鼠模型上对CIA的保护作用。30-1000 nM TAT-rFNK给药组对脱发的保护作用呈剂量依赖关系。此外，人版本的FNK(HFNK)与其他PTD多肽融合显示出保护能力。这些结果表明，PTD-FNK具有抗CIA的保护活性，并且不局限于PTD多肽序列或FNK的种类。因此，PTD-FNK代表了一种预防癌症患者CIA的有用方法的潜力。(C)2007 Elsevier Inc.保留所有权利。
Many anticancer drugs attack rapidly dividing cells, including not only malignant cells but also hair follicle cells, and induce alopecia. Chemotherapy-induced alopecia (CIA) is an emotionally distressing side effect of cancer chemotherapy. There is currently no useful preventive therapy for CIA. We have previously constructed anti-death rFNK protein from rat Bcl-x(L) by site-directed mutagenesis to strengthen cytoprotective activity. When fused to the protein transduction domain (PTD) of HIV/Tat, the fusion protein PTD (TAT)-rFNK successfully entered cells from the outside in vitro and in vivo to exhibit anti-death activity against apoptosis and necrosis. Here, we show that topical application of FNK protected against CIA in a newborn rat model. The protective activity against hair-loss was observed in 30-1000 nM TAT-rFNK administrative groups in a dose-dependent manner. Furthermore, a human version of FNK (hFNK) fused to other PTD peptides exhibited a protective ability. These results suggest that PTD-FNK possesses protective activity against CIA and is not restricted to a sequence of PTD peptides or species of FNK. Thus, PTD-FNK represents potential to develop a useful method for preventing CIA in cancer patients. (c) 2007 Elsevier Inc. All rights reserved.