Benzyl Isothiocyanate: Double Trouble for Breast Cancer Cells
Benzyl Isothiocyanate: Double Trouble for Breast Cancer Cells
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DOI：
10.1158/1940-6207.capr-13-0242
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发表时间：
2013-07
影响因子：
3.3
通讯作者：
C. Rao
中科院分区：
文献类型：
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作者：
C. Rao
对于不同类型的恶性肿瘤，包括乳腺癌，饮食中十字花科蔬菜的摄入量与癌症风险之间已经建立了负相关。十字花科蔬菜的抗癌作用归因于含有异硫氰酸酯(ITC)官能团的化学物质。过去三十年的研究已经提供了广泛的临床前证据，证明了各种ITC在临床前模型中对癌症的疗效。异硫氰酸苄酯(BITC)是一种能够抑制化学诱导的癌症、致癌驱动的肿瘤形成和在啮齿动物癌症模型中移植于人的肿瘤的化合物。先前的工作也证实了BITC有能力影响致癌物质的代谢和与肿瘤进展和侵袭相关的信号通路。在这一期中，Kim和他的同事们展示了BITC在体外和体内都抑制了乳腺癌干细胞的生长，并与抑制全长受体酪氨酸激酶RON及其激活的截断形式(SfRon)有关，这两者似乎都促进了乳腺癌细胞的干化。过表达RON或sfRON可阻止BITC效应。这些数据补充了该小组之前的工作，表明BITC给药通过肿瘤细胞凋亡消除了乳腺肿瘤细胞。在BITC的药物浓度下观察到对乳腺癌干细胞的抑制。这一观点简要回顾了BITC的流行病学证据、临床前疗效数据以及分子和细胞机制属性。简要讨论了与BITC临床发展相关的关键问题。癌症预防研究；6(8)；760-3。©2013 AACR。
An inverse association between dietary intake of cruciferous vegetables and cancer risk has been established for different types of malignancies, including breast cancer. The anticarcinogenic effect of cruciferous vegetables has been attributed to chemicals with an isothiocyanate (ITC) functional moiety. Research over the past three decades has provided extensive preclinical evidence for the efficacy of various ITCs against cancer in preclinical models. Benzyl isothiocyanate (BITC) is one such compound with the ability to inhibit chemically induced cancer, oncogenic-driven tumor formation, and human tumor xenografts in rodent cancer models. Prior work also has established that BITC has the ability to influence carcinogen metabolism and signaling pathways relevant to tumor progression and invasion. In this issue, Kim and colleagues show that BITC inhibits breast cancer stem cell growth, both in vitro and in vivo, in association with suppression of the full-length receptor tyrosine kinase RON as well as its activated truncated form (sfRon), both of which seem to drive stemness in breast cancer cells. Overexpression of RON or sfRon prevented the BITC effect. These data complement prior work from this group showing elimination of mammary tumor cells via tumor cell apoptosis by BITC administration. The inhibition of breast cancer stem cells is observed at pharmacologic concentrations of BITC. This perspective briefly reviews epidemiologic evidence, preclinical efficacy data, and molecular and cellular mechanistic attributes of BITC. Critical issues relevant to clinical development of BITC are discussed briefly. Cancer Prev Res; 6(8); 760–3. ©2013 AACR.