Fatty Acid Synthase Inhibition by Amentoflavone Induces Apoptosis and Antiproliferation in Human Breast Cancer Cells

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概要

• 論文の詳細を見る

• Fatty acid synthase (FASN) is highly expressed in breast carcinomas to support their continuous growth and proliferation, but has low expression level in normal tissues. Considerable interest has been developed in searching for novel FASN inhibitors as a therapeutic target for breast cancer. In present study, amentoflavone was isolated from Selaginella tamariscina, a traditional oriental medicine that has been used to treat cancer for many years, and was found to significantly inhibit the in vitro enzymatic activity of FASN at concentrations above 50 μM. Amentoflavone was also found to decrease fatty acid synthesis by the reduction of [3H]acetyl-CoA incorporation into lipids in FASN-overexpressed SK-BR-3 human breast cancer cells. Furthermore, this study showed that amentoflavone, at a concentration greater than 75 μM, increased the cleavage-activity of caspase-3 and poly (ADP-ribose) polymerase (PARP), and administration of pan-caspase inhibitor Z-VAD-FMK completely rescued the SK-BR-3 cells from PARP cleavages. The sequential internucleosomal DNA fragmentation in SK-BR-3 cells was observed at a concentration of 100 μM. A decrease in breast cancer cell growth was observed in SK-BR-3 cells at 12 and 24 h post treatment with 100 μM of amentoflavone, followed by a dramatic suppression after 48 h. The inhibition of cancer-growth by amentoflavone was dose-dependent, showing a slight reduction at 50 μM and significant reduction at concentrations of 75 and 100 μM. FASN-nonexpressed NIH-3T3 normal cell growth was not decreased by amentoflavone-treatment, both in time- and dose-dependent manners. These data provide evidence that amentoflavone isolated from S. tamariscina induced breast cancer apoptosis through blockade of fatty acid synthesis.

• 日本薬学会の論文

著者

• Lee Jin

  Department of Internal Medicine, Ewha Womans University School of Medicine and Ewha Medical Research

• LEE Myung

  Department of Physics & Astronomy, FPRD, Seoul National University

• OH Won

  College of Pharmacy, Chosun University

• Sul Ji

  Department of Surgery, Chungnam National University Hospital

• Oh Won

  College Of Pharmacy Chosun University

• Lee Myung

  Department Of Family Medicine Brain Korea 21 Project Medical Science College Of Medicine Korea Unive

• Lee Jin

  Department Of Bioscience And Biotechnology Silla University

• Lee Myung

  Department Of Electronic Engineering Kyung-hee University

• Lee Jin

  Department Of Biology Inha University

• Sul Ji

  Department of Surgery and Research Institute for Medicinal Sciences, Chungnam National University School of Medicine

• Lee Myung

  Department of Biomicrosystem, Korea University, Seoul 136-713, Republic of Korea

• LEE Jin

  Department of Biochemistry, College of Medicine, Inje University

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