Effect of luteolin on the methylation status of the OPCML gene and cell growth in breast cancer cells

Dong,Xinmin; Zhang,Jian; Yang,Fan; Wu,Jing; Cai,Rui; Wang,Tian; Zhang,Jiren

doi:10.3892/etm.2018.6526

Effect of luteolin on the methylation status of the OPCML gene and cell growth in breast cancer cells

Authors:
- Xinmin Dong
- Jian Zhang
- Fan Yang
- Jing Wu
- Rui Cai
- Tian Wang
- Jiren Zhang
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Affiliations: Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, P.R. China, Department of Radiotherapy, The Affiliated People's Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia 010017, P.R. China, Department of Basic Medicine, Xiangnan University, Chenzhou, Hunan 423000, P.R. China, Department of Hematology and Oncology, Yan'an People's Hospital, Yan'an, Shaanxi 716000, P.R. China
Published online on: July 26, 2018 https://doi.org/10.3892/etm.2018.6526
Pages: 3186-3194

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Abstract

The present study aimed to investigate the effect of luteolin on the methylation of opioid binding protein/cell adhesion molecule (OPCML) in breast cancer cells, as well as its underlying mechanism of action. Human breast cancer cell lines BT474 and MCF‑7 were cultured in RPMI‑1640 medium supplemented with 10% fetal bovine serum. The cells were treated with 0‑30 µmol/l luteolin prior to investigation. Reverse transcription‑quantitative polymerase chain reaction and western blot analysis were used to determine the mRNA and protein expression, respectively. High performance liquid chromatography and electrosprary ionization‑mass spectrometry was used to analyze the methylation of the OPCML promoter region and whole genome. The methylation activity in the cell nucleus was determined using a DNA methyltransferase catalytic test. ELISA analysis was used to detect changes in the activity of transcription factors Sp1 and nuclear factor (NF)‑κB. An MTT assay was performed to determine cell proliferation, while flow cytometry was used to detect cell cycle stage and apoptosis. Luteolin effectively upregulated the expression of OPCML in breast cancer cells. Luteolin activated OPCML by reducing intracellular methylation levels. Luteolin downregulated intracellular methylation levels by decreasing Sp1 and NF‑κB activities. Luteolin affected the expression of DNMT1 and OPCML by downregulating Sp1 activity. Luteolin inhibited the proliferation and induced the apoptosis of BT474 and MCF‑7 cells. The results of the present study suggest that luteolin inhibits the growth of breast cancer cells by decreasing the methylation and upregulating the expression of the OPCML gene.

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