The chalcone butein from Rhus verniciflua Stokes inhibits clonogenic growth of human breast cancer cells co-cultured with fibroblasts

BACKGROUND: Butein (3,4,2',4'-tetrahydroxychalone), a plant polyphenol, is a major biologically active component of the stems of Rhus verniciflua Stokes. It has long been used as a food additive in Korea and as an herbal medicine throughout Asia. Recently, butein has been shown to suppress the functions of fibroblasts. Because fibroblasts are believed to play an important role in promoting the growth of breast cancer cells, we investigated the ability of butein to inhibit the clonogenic growth of small numbers of breast cancer cells co-cultured with fibroblasts in vitro. METHODS: We first measured the clonogenic growth of small numbers of the UACC-812 human breast cancer cell line co-cultured on monolayers of serum-activated, human fibroblasts in the presence of butein (2 μg/mL) or various other modulators of fibroblast function (troglitazone-1 μg/mL; GW9662-1 μM; meloxican-1 μM; and 3,4 dehydroproline-10 μg/mL). In a subsequent experiment, we measured the dose-response effect on the clonogenic growth of UACC-812 breast cancer cells by pre-incubating the fibroblasts with varying concentrations of butein (10 μg/ml-1.25 μg/mL). Finally, we measured the clonogenic growth of primary breast cancer cells obtained from 5 clinical specimens with normal fibroblasts and with fibroblasts that had been pre-treated with a fixed dose of butein (2.5 μg/mL). RESULTS: Of the five modulators of fibroblast function that we tested, butein was by far the most potent inhibitor of clonogenic growth of UACC-812 breast cancer cells co-cultured with fibroblasts. Pre-treatment of fibroblasts with concentrations of butein as low as 2.5 μg/mL nearly abolished subsequent clonogenic growth of UACC-812 breast cancer cells co-cultured with the fibroblasts. A similar dose of butein had no effect on the clonogenic growth of breast cancer cells cultured in the absence of fibroblasts. Significantly, clonogenic growth of the primary breast cancer cells was also significantly reduced or abolished when the tumor cells were co-cultured with fibroblasts that had been pre-treated with a fixed dose of butein. CONCLUSION: We conclude that fibroblasts pre-treated with non-toxic doses of butein (a natural herbal compound) no longer support the clonogenic growth of small numbers of primary breast cancer cells seeded into co-cultures. These results suggest that interference with the interaction between fibroblasts and breast cancer cells by the natural herbal compound, butein, should be further investigated as a novel experimental approach for possibly suppressing the growth of micrometastases of breast cancer

Changes in Plasma Membrane Surface Potential of PC12 Cells as Measured by Kelvin Probe Force Microscopy

The plasma membrane of a cell not only works as a physical barrier but also mediates the signal relay between the extracellular milieu and the cell interior. Various stimulants may cause the redistribution of molecules, like lipids, proteins, and polysaccharides, on the plasma membrane and change the surface potential (Φs). In this study, the Φss of PC12 cell plasma membranes were measured by atomic force microscopy in Kelvin probe mode (KPFM). The skewness values of the Φss distribution histogram were found to be mostly negative, and the incorporation of negatively charged phosphatidylserine shifted the average skewness values to positive. After being treated with H2O2, dopamine, or Zn2+, phosphatidylserine was found to be translocated to the membrane outer leaflet and the averaged skewness values were changed to positive values. These results demonstrated that KPFM can be used to monitor cell physiology status in response to various stimulants with high spatial resolution

Dietary chalcones with chemopreventive and chemotherapeutic potential

Chalcones are absorbed in the daily diet and appear to be promising cancer chemopreventive agents. Chalcones represent an important group of the polyphenolic family, which includes a large number of naturally occurring molecules. This family possesses an interesting spectrum of biological activities, including antioxidative, antibacterial, anti-inflammatory, anticancer, cytotoxic, and immunosuppressive potential. Compounds of this family have been shown to interfere with each step of carcinogenesis, including initiation, promotion and progression. Moreover, numerous compounds from the family of dietary chalcones appear to show activity against cancer cells, suggesting that these molecules or their derivatives may be considered as potential anticancer drugs. This review will focus primarily on prominent members of the chalcone family with an 1,3-diphenyl-2-propenon core structure. Specifically, the inhibitory effects of these compounds on the different steps of carcinogenesis that reveal interesting chemopreventive and chemotherapeutic potential will be discussed