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A Novel Target Molecule Therapy for Breast Cancer using Tetrocarcin A(TC-A)

使用 Tetrocarcin A (TC-A) 治疗乳腺癌的新型靶分子疗法

基本信息

批准号：
15591351
负责人：
NAKAJIMA Hiroo
金额：
$ 2.11万
依托单位：
Kyoto Prefectural University of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

Loss of growth control and intrinsic inhibitors of apoptosis may contribute to cancer survival by facilitating the mutations and by promoting resistance to various therapy. Meanwhile, the target molecule therapy against cancer has been widely accepted and various target molecular therapeutic agents are developed. Bcl-2 and Bcl-xL proteins are the member of Bcl-2 family, which have been shown to protect cells from some forms of apoptosis. In addition, overexpression of these molecules is believed to contribute to malignant cells expansion by means of anti-apoptotic effect. Tetrocarcin A(TC-A), on the other hand, a novel anti-tumor antibiotic was isolated from the culture broth of Micromonospora chalcea KY11091 through various procedures. Recently, TC-A was verified as an inhibitor of the anti-apoptotic molecule, Bcl-2 and/or Bcl-xL in T cell lines, and promoted apoptosis through the mitochondrial pathway. Here, we examined the effects of TC-A on Bcl-2 and/or Bcl-xL overexpressed human breast cancer cells such as MDA-231, ZR75-1, and KPL-1. Low concentration (2.5 μM) of TC-A induced typical apoptosis in all these cells via mitochondrial pathway. Western blotting analyses, however, have shown none of effects on these molecules expression. In conclusion, TC-A, anti-biotics, appears to be a novel agent that induces apoptosis on Bcl-2 and/or Bcl-xL overexpressed human breast cancers, while its precise mechanism is unknown. Based on these results, TC-A would become a novel chemotherapeutic agent for chemotherapy resistant human breast cancers.We reported those results of research in the 2003 and 2004 Annual Congress of Japan Surgical Society, and the 2004 Annual Congress of Japanese Breast Cancer Society.

生长控制的丧失和细胞凋亡的内在抑制剂可能通过促进突变和促进对各种治疗的抗性而有助于癌症存活。与此同时，针对癌症的靶向分子治疗已被广泛接受，并且开发了各种靶向分子治疗剂。Bcl-2和Bcl-xL蛋白是Bcl-2家族的成员，已被证明可以保护细胞免受某些形式的凋亡。此外，这些分子的过表达被认为通过抗凋亡作用促进恶性细胞扩增。而Tetrocarcin A（TC-A）是一种新的抗肿瘤抗生素，它是从黄色小单孢菌（Micromonospora chalcea）KY 11091的发酵液中分离得到的。最近，TC-A被证实为T细胞系中抗凋亡分子Bcl-2和/或Bcl-xL的抑制剂，并通过线粒体途径促进凋亡。在这里，我们研究了TC-A对Bcl-2和/或Bcl-xL过表达的人乳腺癌细胞如MDA-231、ZR 75 -1和KPL-1的影响。低浓度（2.5 μM）的TC-A通过线粒体途径诱导上述细胞凋亡。然而，Western印迹分析显示对这些分子的表达没有影响。总之，TC-A，抗生素，似乎是一种新的药物，诱导Bcl-2和/或Bcl-xL过表达的人乳腺癌细胞凋亡，但其确切的机制是未知的。基于这些结果，TC-A将成为一种新的化疗药物，用于治疗化疗耐药的人类乳腺癌，我们在2003年和2004年日本外科学会年会和2004年日本乳腺癌学会年会上报道了这些研究结果。