Formononetin inhibits human bladder cancer cell proliferation and invasiveness via regulation of miR-21 and PTEN

Abstract

The isoflavone formononetin is the main active component of Astragalus membranaceus and possesses anti-tumorigenic properties. However, the role of formononetin in human bladder cancer (BCa) has not been fully elucidated. The aim of the present study was to investigate the anti-tumor effects of formononetin on BCa cells and its potential molecular mechanism. T24 cells were treated with different concentrations of formononetin, and then the cell proliferation was assessed by MTT assay, cell apoptosis by Hoechst 33258 stain assay, cell invasiveness by transwell invasion assay, microRNA-21 (miR-21) expression by real-time PCR and the protein level of phosphatase and tensin homolog (PTEN) and phosphorylated homolog of Akt (p-Akt) by western blotting. The results showed that formononetin significantly inhibited the proliferation of T24 cells in a time- and dose-dependent manner. T24 cells treated with formononetin displayed obvious morphological changes of apoptosis and lower invasiveness. In addition, miR-21 expression was significantly decreased in formononetin-treated T24 cells, followed by increase of PTEN, and down-regulation of p-Akt. Collectively, these results suggest that formononetin exerts an anti-carcinogenic effect on BCa in vitro, which might be due to miR-21-mediated regulation of the PTEN/Akt pathway.

Long noncoding RNA neuroblastoma-associated transcript 1 gene inhibits malignant cellular phenotypes of bladder cancer through miR-21/SOCS6 axis

“…But the effects of miR-21-5p on malignant cellular phenotypes of BC are not very clear. Wu Y reported that formononetin could inhibit the invasiveness of BC cells and decrease the expression of miR-21 20 , but the correlation of miR-21-5p expression and the growth and metastasis of BC was not certain.…”

Formononetin Administration Ameliorates Dextran Sulfate Sodium-Induced Acute Colitis by Inhibiting NLRP3 Inflammasome Signaling Pathway

“…It is one of the major biologically active compounds in a variety of Chinese medicinal herbs, such as astragalus, which has been traditionally used for treatment of diabetes over 2000 years in China. Current research evidences indicated that formononetin played several different effects, such as, anti-inflammatory [ 6 , 7 ], antioxidative [ 8 ], antitumor [ 9 ], and promoting apoptosis [ 10 ]. Lima Cavendish et al confirmed that formononetin has an anti-inflammatory effect on rats with peritonitis [ 6 ] and could protect mice from lipopolysaccharide-induced acute lung injury [ 7 ].…”

Participation of MicroRNAs in the Treatment of Cancer with Phytochemicals

“…As stated in Section 2.1.8 , miR-21 directly modulates PTEN, whose function is to inactivate PI3K/Akt signaling in cancer. As a consequence of the miR-21 inhibition, formononetin and galangin upregulate PTEN levels in bladder and cholangiocarcinoma, respectively, thereby inhibiting cancer aggressiveness [ 42 , 43 ]. In colorectal cancer, gambogic acid induces apoptosis by suppressing miR-21 expression, and the cytotoxicity of gambogic acid is reversed by overexpressing miR-21 [ 44 ].…”