Abstract
The secreted frizzled-related protein 5 gene (SFRP5) that antagonize the Wnt/β-catenin signaling is frequently inactivated by promoter methylation and oncogenic activation of the Wnt signaling pathway is common in many cancers. The curcumin-rich Curcuma longa has been reported to potent anti-cancer property involved in epigenetic regulation to inhibit tumor suppressor gene methylation and re-expression. In a compounds screening, we found that curcumin can inhibit Wnt/β-catenin signaling. Therefore, the aim of this study was to investigate the effects of curcumin on SFRP5 DNA methylation modification in an ovarian cancer cell line (SKOV3). SKOV3 cells were treated with DMSO, 10 μM 5-aza-2′-deoxycytidine (DAC), 5 μM DAC, 20 μM curcumin, and 20 μM curcumin combined with 5 μM DAC for 96 hours, following which RNA and proteins were extracted for further analysis. The results showed that curcumin combined with 5 μM DAC may inhibit cancer cell colony formation, migration through EMT (epithelial–mesenchymal transition) process regulation, total DNMT activity, especially in DNMT3a protein expression, and may also regulate tumor suppressor gene SFRP5 expression involved in the Wnt/β-catenin signaling pathway. The combined treatment attenuated ovarian cancer development.
Highlights
The secreted frizzled-related protein 5 gene (SFRP5) that antagonize the Wnt/β-catenin signaling is frequently inactivated by promoter methylation and oncogenic activation of the Wnt signaling pathway is common in many cancers
The inhibition effect on cell growth of combined treatment with 5 μM DAC and 20 μM curcumin was superior to the effects of single treatments (Fig. 1B)
We conducted an investigation of SFRP5 expression variation upon combined treatment with 7.5 μM or 5 μM DAC and 20 μM curcumin using RT-PCR, and found that 5 μM DAC and 20 μM curcumin obviously changed the expression from no signal band to a slight signal band (Fig. 2A,C)
Summary
The secreted frizzled-related protein 5 gene (SFRP5) that antagonize the Wnt/β-catenin signaling is frequently inactivated by promoter methylation and oncogenic activation of the Wnt signaling pathway is common in many cancers. The results showed that curcumin combined with 5 μM DAC may inhibit cancer cell colony formation, migration through EMT (epithelial–mesenchymal transition) process regulation, total DNMT activity, especially in DNMT3a protein expression, and may regulate tumor suppressor gene SFRP5 expression involved in the Wnt/β-catenin signaling pathway. Aberrant Wnt signaling is present in many cancers, including breast, colorectal, prostate and ovarian cancers[12] It is composed of three different molecular pathways, one of which is the canonical pathway, called the Wnt/β-catenin signaling pathway, which is dependent on a stable β-catenin structure; target genes may lead to proliferation and EMT in cancer cells[13]. In the light of this, lower doses are prescribed to minimize the toxicity of DAC; otherwise, improvement of the chemosensitivity of cancer cells is necessary
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