alpha-Tocopheryloxybutyric acid enhances necrotic cell death in breast cancer cells treated with chemotherapy agent.
The overexpression of HER-2 receptor contributes to malignant transformation of breast cancer cells. We have reported that alpha-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 IC(50). 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.
Department of Veterinary Pharmacology, College of Bioresource Sciences, Nihon University, Kanagawa 252-8510, Japan.
Kazuhiro
K
Nishikawa
Haruna
H
Satoh
Ayako
A
Hirai
Kazuyuki
K
Suzuzki
Ryuji
R
Asano
Itsumaro
I
Kumadaki
Kiyokazu
K
Hagiwara
Tomohiro
T
Yano
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D009336:Necrosis; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D020893:Receptor, ErbB-3 / Q000187:drug effects / Q000378:metabolism; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D011518:Proto-Oncogene Proteins; C113106:tocopheryloxybutyric acid; D014810:Vitamin E; D004317:Doxorubicin; D020893:Receptor, ErbB-3; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt