α-Tocopheryloxybutyric acid enhances necrotic cell death in breast cancer cells treated with chemotherapy agent

Nishikawa, Kazuhiro; Satoh, Haruna; Hirai, Ayako; Suzuzki, Kazuyuki; Asano, Ryuji; Kumadaki, Itsumaro; Hagiwara, Kiyokazu; Yano, Tomohiro

doi:10.1016/S0304-3835(03)00462-2

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Volume 201, Issue 1 , Pages 51-56, 10 November 2003

α-Tocopheryloxybutyric acid enhances necrotic cell death in breast cancer cells treated with chemotherapy agent

Kazuhiro Nishikawa
- Department of Veterinary Pharmacology, College of Bioresource Sciences, Nihon University, Kanagawa 252-8510, Japan
Haruna Satoh
- Department of Food Science Research for Health, National Institute of Health and Nutrition, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8636, Japan
Ayako Hirai
- Department of Veterinary Pharmacology, College of Bioresource Sciences, Nihon University, Kanagawa 252-8510, Japan
Kazuyuki Suzuzki
- Department of Veterinary Pharmacology, College of Bioresource Sciences, Nihon University, Kanagawa 252-8510, Japan
Ryuji Asano
- Department of Veterinary Pharmacology, College of Bioresource Sciences, Nihon University, Kanagawa 252-8510, Japan
Itsumaro Kumadaki
- Faculty of Pharmaceutical Sciences, Setsunan University, Osaka 573-0101, Japan
Kiyokazu Hagiwara
- Department of Food Science Research for Health, National Institute of Health and Nutrition, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8636, Japan
Tomohiro Yano
- Department of Food Science Research for Health, National Institute of Health and Nutrition, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8636, Japan
- Corresponding author. Tel.: +81-33203-8063; fax: +81-33205-6549

Received 15 April 2003; received in revised form 25 June 2003; accepted 26 June 2003.

Abstract

The overexpression of HER-2 receptor contributes to malignant transformation of breast cancer cells. We have reported that α-tocopheryloxybutyric acid (TE), non-antioxidative vitamin E ether derivative inhibits the activation of HER-2 receptor. The present study was undertaken to estimate if TE could act as a useful anti-cancer agent against a breast cancer cell overexpressing HER-2 receptor (MDA-MB-453 cell line) in combination with a conventional chemotherapy agent, adriamycin (ADR). TE enhanced cytotoxic effect of ADR against the human breast cancer cell at low doses less than IC₅₀. The enhancing effect was mainly dependent on the elevation of necrotic-like cell death but not apoptotic cell death. In conjugation with this event, the inactivation of HER-2 receptor in the breast cancer cell was caused by the combination of TE with ADR. These results suggest that TE enhances necrotic-like cell death in the breast cancer cells and that the cell death relates to the inactivation of HER-2 receptor in the breast cancer cells.

Keywords: Vitamin E ether derivative, Adriamycin, Breast cancer, HER-2 receptor, Necrotic-like cell death