title: 24-Methylenecycloartanyl ferulate, a major compound of γ-oryzanol, promotes parvin-beta expression through an interaction with peroxisome proliferator-activated receptor-gamma 2 in human breast cancer cells.
abstract: Parvin-β is an adaptor protein that binds to integrin-linked kinase (ILK) and is significantly downregulated in breast tumors and breast cancer cell lines. We treated the breast cancer cell line MCF7 with 24-methylenecycloartanyl ferulate (24-MCF), a γ-oryzanol compound. We observed upregulation of parvin-β (GenBank Accession No. AF237769) and peroxisome proliferator-activated receptor (PPAR)-γ2 (GenBank Accession No. NM_015869). Among γ-oryzanol compounds, only treatment with 24-MCF led to the formation of reverse transcription-PCR products of parvin-β (650 and 500 bp) and PPAR-γ2 (580 bp) in MCF7 cells, but not in T47D, SK-BR-3, or MDA-MB-231 cells. 24-MCF treatment increased the mRNA and protein levels of parvin-β in MCF7 cells in a dose-dependent manner. We hypothesized that there is a correlation between parvin-β expression and induction of PPAR-γ2. This hypothesis was investigated by using a promoter-reporter assay, chromatin immunoprecipitation, and an electrophoretic mobility shift assay. 24-MCF treatment induced binding of PPAR-γ2 to a peroxisome proliferator response element-like cis-element (ACTAGGACAAAGGACA) in the parvin-β promoter in MCF7 cells in a dose-dependent manner. 24-MCF treatment significantly decreased anchorage-independent growth and inhibited cell movement in comparison to control treatment with dimethyl sulfoxide. 24-MCF treatment reduced the levels of GTP-bound Rac1 and Cdc42. Evaluation of Akt1 inhibition by 24-MCF revealed that the half maximal effective concentration was 33.3 μM. Docking evaluations revealed that 24-MCF binds to the ATP-binding site of Akt1(PDB ID: 3OCB) and the compound binding energy is -8.870 kcal/mol. Taken together, our results indicate that 24-MCF treatment increases parvin-β expression, which may inhibit ILK downstream signaling.
authors.affiliation: Department of Agro-Food Resources, National Academy of Agricultural Science, Rural Department Administration, Wanju-gun, Jeollabuk-do 565-851, Republic of Korea.
authors.forename: Heon Woong
authors.initials: HW
authors.lastname: Kim
authors.affiliation: Department of Agro-Food Resources, National Academy of Agricultural Science, Rural Department Administration, Wanju-gun, Jeollabuk-do 565-851, Republic of Korea.
authors.forename: Eun Joung
authors.initials: EJ
authors.lastname: Lim
authors.affiliation: Department of Agro-Food Resources, National Academy of Agricultural Science, Rural Department Administration, Wanju-gun, Jeollabuk-do 565-851, Republic of Korea.
authors.forename: Hwan Hee
authors.initials: HH
authors.lastname: Jang
authors.affiliation: Research Institute of Medical Science, KonKuk University, School of Medicine, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea.
authors.forename: XueLei
authors.initials: X
authors.lastname: Cui
authors.affiliation: Department of Infection & Immunology, School of Medicine, KonKuk University 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea.
authors.forename: Da Rae
authors.initials: DR
authors.lastname: Kang
authors.affiliation: Department of Agro-Food Resources, National Academy of Agricultural Science, Rural Department Administration, Wanju-gun, Jeollabuk-do 565-851, Republic of Korea.
authors.forename: Sung Hyen
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Agro-Food Resources, National Academy of Agricultural Science, Rural Department Administration, Wanju-gun, Jeollabuk-do 565-851, Republic of Korea.
authors.forename: Haeng Ran
authors.initials: HR
authors.lastname: Kim
authors.affiliation: Department of Agro-Food Resources, National Academy of Agricultural Science, Rural Department Administration, Wanju-gun, Jeollabuk-do 565-851, Republic of Korea.
authors.forename: Jeong Sook
authors.initials: JS
authors.lastname: Choe
authors.affiliation: Department of Pathology, School of Medicine and Institute of Biomedical Science and Technology, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Young Mok
authors.initials: YM
authors.lastname: Yang
authors.affiliation: Department of Agro-Food Resources, National Academy of Agricultural Science, Rural Department Administration, Wanju-gun, Jeollabuk-do 565-851, Republic of Korea. Electronic address: jungbkim@korea.kr.
authors.forename: Jung Bong
authors.initials: JB
authors.lastname: Kim
authors.affiliation: Research Institute of Medical Science, KonKuk University, School of Medicine, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea. Electronic address: nihpark@yahoo.com.
authors.forename: Jong Hwan
authors.initials: JH
authors.lastname: Park
mesh_terms: D000185:Actinin / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D003373:Coumaric Acids / Q000008:administration & dosage*; D006801:Humans; D061986:MCF-7 Cells; D047495:PPAR gamma / Q000378:metabolism*; D010666:Phenylpropionates / Q000008:administration & dosage*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D003373:Coumaric Acids; C486591:PARVB protein, human; D047495:PPAR gamma; D010666:Phenylpropionates; D000185:Actinin; C004999:ferulic acid; C013172:gamma-oryzanol
keywords: 24-Methylenecycloartanyl ferulate; Akt1; Integrin-linked kinase; PPAR-γ2; Parvin-β