Background: The common plant bioflavonoid, quercetin, is cytotoxic to various tumor cell lines, particularly breast cancer, by affecting the protein-kinase-C-dependent signal pathways and by cell cycle regulation. However, its role in breast cancer metastasis has not been studied so far. Increased uPA activity is evident in highly metastatic breast cancer, which is calcium dependent. Methods: MDA MB 231 cells were treated with various concentrations of quercetin (15–45 µg/ml). The cytotoxic effect of quercetin was assessed by MTT assay and DNA fragmentation analysis. Intracellular calcium levels were measured using Fura-2, a specific Ca2+ fluorescence indicator. Calcium uptake and release in cells treated with quercetin were measured using radioactive 45Ca2+. Urokinase enzyme activity was assayed by a casein zymogram. Results: Quercetin elicited dose- and time-dependent cytotoxicity as evidenced by the MTT assay. The maximum effect was observed at 48 h with a quercetin concentration of (45 µg/ml). DNA agarose gel electrophoresis showed dose-dependent DNA fragmentation on quercetin treatment. Quercetin caused significant depletion of cytosolic calcium levels and decreased calcium uptake from the intracellular stores. Casein zymogram showed a marked reduction of urokinase activity as evident by clear lysis bands on a dark background on treatment with quercetin. Conclusion: Quercetin was found to exhibit cytotoxicity in the highly invasive breast cancer cell line MDA MB 231 in a dose- and time-dependent manner. Quercetin inhibited calcium dependent urokinase activity and hence may prove to be an effective antimetastatic agent.
Background: Breast cancer chemotherapy aims at employing cytotoxic agents that swing the balance between tumor cell invasion and host immune cells in favor of the latter. This study aimed at assessing the effect of exogenous histone H1 in maintaining the immune status of animals in experimental breast cancer taking advantage of its tumor-suppressive activity. Methods: Histone H1 was injected intratumorally as a single injection in tumor-bearing animals. Tumor response was assessed from changes in tumor volume, survival time and the immune status of animals from total and differential blood cell counts, levels of circulating immune complexes, thromboxane B2 and IgA in serum. Immune response was assessed from the macrophage count in the tumor and peritoneal exudates after activation. Results: Histone H1 treatment significantly inhibited tumor growth, enhanced mean survival time and significantly improved the immune response and status. Conclusion: These results indicate that histone H1 plays a vital role in maintaining the immune status.
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