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

  • Biochem Biophys Res Commun. 2015 Dec 25;468(4):574-9. doi: 10.1016/j.bbrc.2015.10.147.
Heon Woong Kim  1 ,  Eun Joung Lim  1 ,  Hwan Hee Jang  1 ,  XueLei Cui  2 ,  Da Rae Kang  3 ,  Sung Hyen Lee  1 ,  Haeng Ran Kim  1 ,  Jeong Sook Choe  1 ,  Young Mok Yang  4 ,  Jung Bong Kim  5 ,  Jong Hwan Park  6
Affiliations
  • 1. Department of Agro-Food Resources, National Academy of Agricultural Science, Rural Department Administration, Wanju-gun, Jeollabuk-do 565-851, Republic of Korea.
  • 2. Research Institute of Medical Science, KonKuk University, School of Medicine, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea.
  • 3. Department of Infection & Immunology, School of Medicine, KonKuk University 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea.
  • 4. Department of Pathology, School of Medicine and Institute of Biomedical Science and Technology, Konkuk University, Seoul 143-701, Republic of Korea.
  • 5. Department of Agro-Food Resources, National Academy of Agricultural Science, Rural Department Administration, Wanju-gun, Jeollabuk-do 565-851, Republic of Korea. Electronic address: [email protected].
  • 6. Research Institute of Medical Science, KonKuk University, School of Medicine, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea. Electronic address: [email protected].
PMID: 26549231 DOI: 10.1016/j.bbrc.2015.10.147
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.

Keywords
24-Methylenecycloartanyl ferulate; Akt1; Integrin-linked kinase; PPAR-γ2; Parvin-β.
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