Genistein, a soy isoflavone, enhances necrotic-like cell death in a breast cancer cell treated with a chemotherapeutic agent.
Genistein is a major component of soybean isoflavone and has preventive effect against breast cancer. In breast cancer, the over-expression of HER-2 contributes to malignant transformation of the cancer cells. The present study was undertaken to estimate if genistein could act as a useful anti-cancer agent against a breast cancer cell overexpressing HER-2 in combination with a conventional chemotherapy agent, adriamycin (ADR). Genistein enhanced cytotoxic effect of ADR at low doses less than IC50 against the human breast cancer cell. The enhancing effect was mainly dependent on the elevation of necrotic-like cell death but not apoptotic cell death. In conjugation with this event, remarkable inactivation of HER-2 and Akt in the breast cancer cell was caused by the combination of genistein and ADR. These results suggest that genistein enhances necrotic-like cell death of the breast cancer cells through the inactivation of HER-2 receptor and Akt in combination with ADR.
Satoh
Haruna
H
Department of Food Science Research for Health, National Institute of Health and Nutrition, Tokyo 162-8636, Japan.
Nishikawa
Kazuhiro
K
Suzuki
Kazuyuki
K
Asano
Ryuji
R
Virgona
Nantiga
N
Ichikawa
Tomio
T
Hagiwara
Kiyokazu
K
Yano
Tomohiro
T
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000627:therapeutic use*; D004347:Drug Interactions; D018734:Genes, erbB-2 / Q000187:drug effects*; D019833:Genistein / Q000627:therapeutic use*; D006801:Humans
D000970:Antineoplastic Agents; D004317:Doxorubicin; D019833:Genistein