Lucidin 3-methyl ether from Rubia philippinensis suppresses the proliferation of multiple myeloma cells through the promotion of ß-catenin degradation.

BACKGROUND: Constitutive accumulation of ß-catenin has been frequently observed in multiple myeloma. Extracts from genus Rubia plants exhibit cytotoxic activity against several types of cancer cells; however, little is known about their chemopreventive mechanisms and bioactive metabolites. PURPOSE: Purpose: The study aimed to identify the underlying antiproliferative mechanisms of Rubia philippinensis extract in multiple myeloma cells and the major active metabolites responsible for cytotoxic activity of R. philippinensis. METHODS: The effects of R. philippinensis extracts and lucidin 3-methyl ether on the Wnt/ß-catenin pathway were determined by cell-based reporter assay, Western blot analysis, and RT-PCR. The antiproliferative activity was evaluated by cell viability assay and apoptosis analysis in RPMI8226 and MM.1S multiple myeloma cells. RESULTS: R. philippinensis extracts inhibited Wnt/ß-catenin signaling and lucidin 3-methyl ether, an anthraquinone derivative, was identified as the major active metabolite responsible for the inhibition of Wnt/ß-catenin signaling. Lucidin 3-methyl ether induced ß-catenin phosphorylation at Ser33/Ser37/Thr41 residues and promoted proteasomal degradation of ß-catenin via a GSK-3ß-independent mechanism, thereby downregulating Wnt3a-induced ß-catenin response transcription (CRT). Moreover, lucidin 3-methyl ether repressed the expression of ß-catenin/T-cell factor (TCF)-dependent genes, such as cyclin D1, c-myc, and axin-2, thus inhibiting MM cell proliferation. Apoptosis was also elicited by lucidin 3-methyl ether, as indicated by the increase in the population of annexin V-FITC positive cells and caspase-3/7 activity in MM cells. CONCLUSION: These findings indicate that R. philippinensis and its active metabolite lucidin 3-methyl ether prevent cell proliferation through the suppression of the Wnt/ß-catenin pathway and exhibit potential as chemopreventive agents for the treatment of MM.

Root Bark of Morus alba L. and Its Bioactive Ingredient, Ursolic Acid, Suppress the Proliferation of Multiple Myeloma Cells by Inhibiting Wnt/ß-Catenin Pathway.

The root bark of Morus alba L. has cytotoxic activity against several types of cancer cells. However, little is known about its chemopreventive mechanisms and bioactive metabolites. In this study, we showed that M. alba L. root bark extracts (MRBE) suppressed ß-catenin response transcription (CRT), which is aberrantly activated in various cancers, by promoting the degradation of ß-catenin. In addition, MRBE repressed the expression of the ß-catenin/T-cell factor (TCF)-dependent genes, cmyc and cyclin D1, thus inhibiting the proliferation of RPMI-8226 multiple myeloma (MM) cells. MRBE induced apoptosis in MM cells, as evidenced by the increase in the population of annexin VFITC- positive cells and caspase-3/7 activity. We identified ursolic acid in MRBE through LC/mass spectrum (MS) and observed that it also decreased intracellular ß-catenin, c-myc, and cyclin D1 levels. Furthermore, it suppressed the proliferation of RPMI-8226 cells by stimulating cell cycle arrest and apoptosis. These findings suggest that MRBE and its active ingredient, ursolic acid, exert antiproliferative activity by promoting the degradation of ß-catenin and may have significant chemopreventive potential against MM.

Multi-Color Luminescence Transition of Upconversion Nanocrystals via Crystal Phase Control with SiO2 for High Temperature Thermal Labels.

Upconversion nanocrystals (UCNs)-embedded microarchitectures with luminescence color transition capability and enhanced luminescence intensity under extreme conditions are suitable for developing a robust labeling system in a high-temperature thermal industrial process. However, most UCNs based labeling systems are limited by the loss of luminescence owing to the destruction of the crystalline phase or by a predetermined luminescence color without color transition capability. Herein, an unusual crystal phase transition of UCNs to a hexagonal apatite phase in the presence of SiO2 nanoparticles is reported with the enhancements of 130-fold green luminescence and 52-fold luminance as compared to that of the SiO2-free counterpart. By rationally combining this strategy with an additive color mixing method using a mask-less flow lithography technique, single to multiple luminescence color transition, scalable labeling systems with hidden letters-, and multi-luminescence colored microparticles are demonstrated for a UCNs luminescence color change-based high temperature labeling system.