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Reducing the expression of endothelial cell adhesion molecules (ECAMs) is known to decrease inflammation-induced vascular complications. In this study, we explored whether rhein can reduce the inflammation-induced expression of ECAMs in human umbilical vein endothelial cells (HUVECs) with or without lipopolysaccharide (LPS) stimulation. HUVECs were treated with different concentrations of rhein with or without 2.5 μg/ml LPS stimulation. Cell viability was assayed using the MTT method. Real-time PCR and Western blot analysis were used to measure the transcription and expression levels of ECAMs, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-SELECTIN and related signaling proteins. The results indicated that rhein (0-20 μmol/L) and LPS (0-10 μg/ml) had no effect on the viability of HUVECs. LPS could promote the expression of VCAM-1, ICAM-1 and E-SELECTIN. Rhein appeared to target VCAM-1, ICAM-1 and E-SELECTIN, with the transcription and expression of all three factors being reduced by the rhein treatment (10 and 20 μmol/L). The transcription and expression of VCAM-1 were also reduced by treatment with rhein (10 and 20 μmol/L) in the presence of LPS stimulation. In conclusion, rhein treatment reduced the expression of VCAM-1 in HUVECs via a p38-dependent pathway. [ABSTRACT FROM AUTHOR]

Rhein lysinate (RHL), easily dissolved in water, is one of the anthraquinones, and has been shown to have anti-tumor activity in different human cancer cell lines. In the present study, we observed that RHL could cause vacuolar degeneration in HeLa cells, which was not observed in human umbilical vein endothelial cells (HUVECs) and other cell lines (SKOV-3 and SK-BR-3). Therefore, the purpose of this study was to investigate the anti-tumor effect of rhein lysinate on human cervix cancer HeLa cells. The results indicated that RHL could induce HeLa cell S-phase arrest and RHL (higher than 80 μM) also induced HeLa cell G2/M-phase arrest in a dose-dependent manner. Compared to the HeLa cells, RHL induced HUVECs G1-phase arrest at all dose levels tested in a dose-dependent manner. Treatment with RHL led to a significant S or G2/M-phase arrest through promoting the expression of p53 and p21 and the phosphorylation of p53. Moreover, 80 μM RHL could increase 5-FU anti-tumor activity. In conclusion, RHL could be a novel chemotherapeutic drug candidate for the treatment of human cervix cancer in the future. [ABSTRACT FROM AUTHOR]

In previous studies, rhein, one of the major bioactive constituents in the rhizome of rhubarb, inhibited the proliferation of various human cancer cells. However, because of its water insolubility, the anti-tumor efficacy of rhein was limited in vivo. In this study, we observed the anti-tumor activity of rhein lysinate (the salt of rhein and lysine easily dissolves in water) in vivo and investigated its mechanism. Inhibition of ovarian cancer SKOV-3 cell proliferation was determined by MTT assay and the mechanism of action of rhein lysinate was investigated by Western blot analysis. The therapeutic efficacy of rhein lysinate was evaluated by intragastric and intraperitoneal administrations in H22 hepatocellular carcinoma mice. Rhein lysinate inhibited the proliferation of SKOV-3 cells and the IC50 value was 80 μM. Rhein lysinate inhibited the phosphorylation of MEK and ERK and increased the anti-tumor activity of Taxol in vitro. It inhibited tumor growth by both intragastric and intraperitoneal administrations and improved the therapeutic effect of Taxol in H22 hepatocellular carcinoma mice. In conclusion, rhein lysinate offers an anti-tumor activity in vivo and is hopeful to be a chemotherapeutic drug. [ABSTRACT FROM AUTHOR]