Tricetin

Journal of Agricultural & Food Chemistry, 2009, 57(18):8688-8695.

Tricetin, a dietary flavonoid, inhibits proliferation of human breast adenocarcinoma mcf-7 cells by blocking cell cycle progression and inducing apoptosis.[Reference: WebLink]

This study is the first to investigate the anticancer effect of Tricetin in human breast adenocarcinoma MCF-7 cells.
METHODS AND RESULTS:
Results reveal that Tricetin inhibits MCF-7 cells by blocking cell cycle progression in the G2/M phase and inducing apoptosis. Cell cycle blockade is associated with increased activation of ataxia telangiectasia-mutated (ATM). Activation of ATM by Tricetin phosphorylated p53 at serine 15, resulting in increased stability of p53 by decreasing p53 and murine double minute-2 (MDM2) interaction. In addition, Tricetin-mediated G2/M phase arrest was also associated with decreases in the amounts of cyclin B, cyclin A, cdc2 and cdc25C, and increases in the phosphorylation of Chk2, cdc25C and cdc2. The specific ATM inhibitor caffeine significantly decreased Tricetin-mediated G2/M arrest by inhibiting the phosphorylation of p53 (serine 15) and Chk2. Tricetin-induced apoptotic cell death is associated with changes in the expression of Bax and Bak, decreasing levels of Bcl-2 and Bcl-X(L), and subsequently triggering the mitochondrial apoptotic pathway. In addition, pretreatment of cells with caspase-9 inhibitor blocked Tricetin-induced apoptosis, indicating that caspase-9 activation is involved in Tricetin-mediated MCF-7 cell apoptosis.
CONCLUSIONS:
These findings suggest that Tricetin may be a promising chemopreventive agent against human breast cancer.

Environmental toxicology, 2017, 32(7-8):2032-2040.

Tricetin inhibits human osteosarcoma cells metastasis by transcriptionally repressing MMP-9 via p38 and Akt pathways.[Reference: WebLink]

Tricetin, a dietary flavonoid, has cytostatic properties and anti-metastasis activities in various cancer cells. However, the detailed impacts and underlying mechanisms of Tricetin on human osteosarcoma cell metastasis are still unclear.
METHODS AND RESULTS:
Here, the hypothesis that Tricetin possesses the anti‐metastatic effects on human osteosarcoma cells was tested. The effects of Tricetin on cell viability, motility, migration, and invasion in human osteosarcoma U2OS and HOS cells were investigated. Gelatin zymography, western blotting, polymerase chain reaction (PCR), and the luciferase assay were used to further explore the underlying mechanisms involved in anti‐metastatic effects in U2OS cells. Their results showed that Tricetin, up to 80 uM without cytotoxicity, attenuated U2OS and HOS cells motility, invasiveness, and migration by reducing matrix metalloproteinase (MMP)-9 enzyme activities. In U2OS cells, Tricetin decreased MMP-9 protein and mRNA expressions, which was confirmed by real-time PCR. Next, Tricetin reduced phosphorylation of p38 and Akt, but no effect on phosphorylation of ERK1/2 and JNK.
CONCLUSIONS:
In conclusion, Tricetin possesses the anti‐metastatic activity of osteosarcoma cells by transcriptionally repressing MMP-9 via p38 and Akt signaling pathways. This may be potentially useful as anti‐metastatic agents for osteosarcoma chemotherapy.