title: Luteolin Induces Apoptosis by Up-regulating miR-34a in Human Gastric Cancer Cells.
abstract: Luteolin (39, 49, 5, 7-tetrahydroxyflavone) is a natural flavonoid that exists in several types of vegetables, fruits, and medicinal herbs that inhibits tumorigenesis in different types of cancer. In this study, we demonstrate luteolin-mediated regulation of cell apoptosis in a gastric cancer cell line through inhibition of the apoptosis regulatory protein Bcl-2. MTT and flow cytometric analysis indicate that luteolin inhibits cell proliferation and induces apoptosis in gastric cancer cells. Quantitative real-time polymerase chain reaction (qRT-PCR) revealed that miR-34a expression is downregulated in the majority of human primary gastric cancer tissues (8/12, 66.7%), compared with adjacent, pair-matched non-tumor tissues. Target analysis indicated that micro RNA (miR)-34a directly regulates Bcl-2, and miR-34a overexpression decreased Bcl-2 protein level in gastric cancer cells. We also found that luteolin upregulates miR-34a expression and downregulates Bcl-2 expression. Furthermore, anti-miR-34a oligonucleotides (AMO) partly reverse luteolin-induced Bcl-2 downregulation in gastric cancer cells. Based on these results, we can draw the conclusion that luteolin partly decreases Bcl-2 expression through upregulating miR-34a expression. This study shows for the first time that the miR-34a pathway plays an important role in luteolin-induced apoptosis in gastric cancer cells.
authors.affiliation: Department of Oncology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, PR China Cancer Center of Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, PR China These authors contributed equally to this work.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Geriatrics, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, PR China These authors contributed equally to this work.
authors.forename: Min
authors.initials: M
authors.lastname: Huang
authors.affiliation: Department of Radiation Therapy, Jiangsu Tumor Hospital, Affiliated to Nanjing Medical University, 42 Baiziting Road, Nanjing 210009, PR China.
authors.forename: Yatian
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Oncology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, PR China Cancer Center of Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, PR China.
authors.forename: Yongqian
authors.initials: Y
authors.lastname: Shu
authors.affiliation: Department of Oncology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, PR China Cancer Center of Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, PR China liu-ping@csco.org.cn whdactor@hotmail.com hmdoctor@163.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D047311:Luteolin / Q000494:pharmacology*; D035683:MicroRNAs / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D014162:Transfection; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D047311:Luteolin
keywords: Apoptosis; Bcl-2; Gastric cancer; Luteolin; miR-34a