Luteolin induces apoptotic cell death through AIF nuclear translocation mediated by activation of ERK and p38 in human breast cancer cell lines

• Published in: Cell biology international Vol. 36; no. 4; pp. 339 - 344
• Main Authors: Kim, Moon Jung, Woo, Jae Suk, Kwon, Chae Hwa, Kim, Jae Ho, Kim, Yong Keun, Kim, Ki Hyung
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.04.2012
• Subjects: Antineoplastic Agents - pharmacology; apoptosis; Apoptosis - drug effects; Apoptosis Inducing Factor - genetics; Apoptosis Inducing Factor - metabolism; Breast Neoplasms; caspase; Caspase 3 - genetics; Caspase Inhibitors; caspase; extracellular‐signal‐regulated kinase (ERK); Cell Cycle - drug effects; Cell Line, Tumor; Dose-Response Relationship, Drug; Extracellular Signal-Regulated MAP Kinases - antagonists & inhibitors; Extracellular Signal-Regulated MAP Kinases - genetics; Extracellular Signal-Regulated MAP Kinases - metabolism; extracellular-signal-regulated kinase (ERK); Female; flavonoid; Gene Expression Regulation, Neoplastic - drug effects; Gene Knockdown Techniques; Genetic Vectors; Humans; luteolin; Luteolin - pharmacology; MAP Kinase Signaling System - drug effects; MicroRNAs - genetics; p38; p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors; p38 Mitogen-Activated Protein Kinases - genetics; p38 Mitogen-Activated Protein Kinases - metabolism; Protein Transport - drug effects; Transfection
• ISSN: 1065-6995; 1095-8355
• DOI: 10.1042/CBI20110394

The flavonoid, luteolin, has been shown to have anticancer activity in various cancer cells; however, the precise molecular mechanism of its action is not completely understood, and studies were conducted to find out how it induces apoptosis in breast cancer cells. Luteolin induced a reduction of viability in a dose‐ and time‐dependent manner. The pro‐apoptotic effect of luteolin was demonstrated by cell cycle measurement and Hoechst 3325 staining. Western blot analysis showed that luteolin activates ERK (extracellular‐signal‐regulated kinase) and p38. Pharmacological inhibition or knockdown of ERK and p38 protected against luteolin‐induced cell death; however, the caspase‐3‐specific inhibitor had no effect. Immunocytochemical examination indicated that luteolin induced nuclear translocation of AIF (apoptosis‐inducing factor), which was mediated by activation of ERK and p38. Transfection of a vector expressing the miRNA (microRNA) of AIF prevented luteolin‐induced apoptosis. The data suggest that luteolin induces a caspase‐dependent and ‐independent apoptosis involving AIF nuclear translocation mediated by activation of ERK and p38 in breast cancer cells.