Isoquercitrin isolated from Hyptis fasciculata reduces glioblastoma cell proliferation and changes β-catenin cellular localization

Abstract

Isoquercitrin isolated from the aerial parts of Hyptis fasciculata was evaluated according to its capacity to interfere with glioblastoma (Gbm) cell growth. Gbm cells were incubated with isoquercitrin, quercetin, or rutin at concentrations of 25, 50, and 100 mumol/l for 24, 48, and 72 h. Quercetin and rutin affected Gbm cell proliferation after treatment times of longer than 24 h. However, increasing concentrations of isoquercitrin inhibited 50% of Gbm cell proliferation at 24 h and further reached nearly 90% inhibition at 72 h. This effect did not affect cell morphology, cell viability, or cleaved capase-3 levels, indicating that isoquercitrin did not induce Gbm cell death. A marked reduction in cyclin D1 levels and an increase in p27 levels were observed when 100 micromol/l of isoquercitrin was added to Gbm cells. Interestingly, nuclear beta-catenin staining observed in a subpopulation of untreated Gbm cells was found in the cytoplasm after 100-micromol/l isoquercitrin treatment. Collectively, these data show that isoquercitrin reduces Gbm cell growth without inducing apoptosis, possibly by modulating the control of the cell cycle. Our data also suggest that beta-catenin-mediated signaling may be involved on the antiproliferative activity of isoquercitrin.

Isoquercitrin Suppresses Colon Cancer Cell Growth in Vitro by Targeting the Wnt/β-Catenin Signaling Pathway

“…Our previous study suggested that isoquercitrin changes ␤-catenin cellular localization (16). To test this hypothesis, we conducted a siamois reporter assay (S01234-Lux) for the Wnt/␤-catenin pathway in Xenopus embryos (23).…”

“…These anti-proliferative effects were accompanied by changes in ␤-catenin cellular localization, suggesting that Wnt/␤-catenin signaling might be altered by this flavonoid (16).…”

“…Quercetin is a well known flavonoid with a num- DECEMBER 19, 2014 • VOLUME 289 • NUMBER 51 ber of biological effects that have been well described (15,28). Rutin is a flavonoid that has little effect on tumor cells (3,16). Quercetin impaired cell viability after 12 h of treatment (Fig.…”

“…Our previous data have shown that isoquercitrin, which is derived from quercetin, affects the proliferation of glioblastoma cells, with lower toxicity (16). These anti-proliferative effects were accompanied by changes in ␤-catenin cellular localization, suggesting that Wnt/␤-catenin signaling might be altered by this flavonoid (16).…”

“…The use of Xenopus allows a fast and clear functional reading on the role of small molecules in this signaling pathway (11,15,16). In addition, we monitored cell growth, death, migration, and toxicity of colon cancer cells upon isoquercitrin treatment.…”