Quercetin reverses tamoxifen resistance in breast cancer cells.

PURPOSE: To investigate the effect of quercetin on the reversal of tamoxifen resistance in breast cancer cells, and explore the underlying mechanism. METHODS: We established a tamoxifen-resistant breast cancer cell line (MCF-7Ca/TAM-R), and exposed it to different concentrations of quercetin (experimental group 1: 10 µM, group 2: 25 µM, and group 3: 50µM). Each group was further subdivided into 2 subgroups: 1) simultaneous administration of quercetin and 4-hydroxytamoxifen (OHT); 2) sequential administration of quercetin (12-h induction) followed by OHT. No drug exposure and OHT alone were used as controls. We determined cell survival, apoptosis, and expression of ERα (estrogen receptor α) and Her-2 (human epidermal growth factor receptor 2). RESULTS: With increasing dosage of quercetin, significant decrease in proliferation and increase in apoptosis was observed. Low concentrations of quercetin (10 µM) had no effects. We found no significant difference between simultaneous and sequential mode of drug administration. Further, with increasing dosage of quercetin, we observed a gradual reduction in Her-2 expression and upregulation of ERα. Again, no difference in Her-2 and ERα protein levels between simultaneous and sequential drug administration was noticed. CONCLUSIONS: Proliferation inhibition and apoptosis in MCF-7Ca/TAM-R cells increase with increasing dosage of quercetin. This suggests that quercetin can reverse tamoxifen resistance in breast cancer cells. The underlying mechanism likely involves upregulation of ERα combined with downregulation of Her-2. However, this effect is independent of whether quercetin and tamoxifen are administered simultaneously or sequentially.

Metformin inhibits proliferation and promotes apoptosis of HER2 positive breast cancer cells by downregulating HSP90.

PURPOSE: To investigate the effects and the possible molecular mechanisms of metformin on HER2 positive breast cancer cells. METHODS: SK-BR-3 HER2 positive breast cancer cells were treated with different concentrations of metformin. The growth inhibitory rate of the cells was calculated by MTT assay, apoptosis was detected by flow cytometry, and the expression level of heat shock protein 90 (HSP90) was performed by Western blot analysis. A control group consisted of cells treated with PBS. RESULTS: With increased concentrations of metformin, cell growth inhibitory rates increased. The growth inhibitory rates with 0.5 mM, 2mM or 8mM metformin were significantly higher compared with the control group (p<0.05). Apoptosis in the metformin treated cells was also significantly higher compared with the control group (p=0.003). The expression level of HSP90 in the metformin group was significantly lower than that in the control group. CONCLUSION: Metformin can inhibit the proliferation and promote apoptosis of HER2 positive breast cancer cells,which is maybe related to inhibition of HSP90.

CXCR7 functions in colon cancer cell survival and migration.

C-X-C chemokine receptor 7 (CXCR7) is a known promoter of tumor progression and metastasis; however, little is known about its role in colon cancer. The aim of the present study was to investigate the function of CXCR7 in human colon cancer cells. CXCR7 mRNA levels were examined in HT-29 and SW-480 human colon cancer cell lines using a quantitative polymerase chain reaction. CXCR7-knockdown was performed with small interfering RNA and lentiviral-mediated gene delivery. Immunofluorescence (IF) was conducted to examine CXCR7 expression and localization in colon cancer cells. Cell survival and migration were evaluated using MTT and migration assays, respectively. HT-29 cells expressed higher levels of CXCR7 mRNA and were therefore used in subsequent experiments. IF staining revealed that the CXCR7 protein was expressed on the cell membrane, and its expression decreased following CXCR7-short hairpin RNA lentiviral transfection. Lentiviral CXCR7-knockdown resulted in decreased cell survival and migration; however, MTT assays revealed that the lentiviral vector itself was cytotoxic. This cytotoxicity was indicated as the cell survival of the negative control group cells was significantly decreased compared with that of the blank control group cells (P<0.05). In conclusion, it is becoming increasingly evident that CXCR7 plays a role in colon cancer promotion, suggesting that CXCR7 is a promising biomarker for chemokine receptor-based drug development. Furthermore, the fact that CXCR7 is expressed on the membrane and not intracellularly makes it a prime target for drug-based intervention.

Inhibitory effects of water caltrop pericarps on the growth of human gastric cancer cells in vitro.

Water caltrop is a popular traditional vegetable in China, and its pericarps are always wasted. In the present work reported here, pericarps from three different Chinese water caltrop cultivars were collected and extracted using 70% methanol and hot water. All the extracts contained significant amounts of polyphenols (183.7-201.7 mg GAE/g), flavonoids (34.3-54.6 mg RE/g) and saponins (23.2- 36.3 mg GRE/g). These extracts exhibited strong antioxidant capacity as assessed by DPPH, ABTS and FRAP methods. High correlations were found in DPPH, ABTS and polyphenols, FRAP and saponins. All the three extracts inhibited proliferation of SGC7901 human gastric cancer cells and HepG2 human hepatocarcinoma cells in a dose dependent manner without detectable cytotoxicity on HUVEC normal cells. Flow cytometry showed that apoptosis of SGC7901 and HepG2 cells was induced by water caltrop extracts while HUVEC cells were relatively resistant to apoptosis. Hot water extracts showed similar bioactivities as methanol extracts, which indicated that hot water could be used to extract bioactive compounds instead of organic solvents. These results suggest that water caltrop pericarps could be explored for their potential as anti-cancer drugs in future studies.