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

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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.