Rhein lysinate suppresses the growth of breast cancer cells and potentiates the inhibitory effect of Taxol in athymic mice

Abstract

Earlier studies have shown that rhein, one of the major bioactive constituents of the rhizome of rhubarb, inhibits the proliferation of various human cancer cells. However, because of its water insolubility, the antitumor efficacy of rhein is limited in vivo. In this study, we studied the antitumor activity of rhein lysinate (the salt of rhein and lysine and easily dissolving in water) and its mechanism. Inhibition of breast cancer 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 human cancer xenografts in athymic nude mice. Rhein lysinate inhibited the proliferation of breast cancer cells (MCF-7, SK-Br-3, and MDA-MB-231). The IC50 values were 95, 80, and 110 micromol/l, respectively. Rhein lysinate inhibited the phosphorylation of epidermal growth factor receptor, MEK, and ERK with or without EGF stimulation. It also inhibited tumor growth and enhanced the therapeutic effect of Taxol on MCF-7 xenografts in athymic mice. Rhein lysinate inhibited the phosphorylation of epidermal growth factor receptor and MAPK signal pathway. These results suggest that rhein lysinate might be useful as a modulation agent in cancer chemotherapy.

Rhein lysinate inhibits cell growth by modulating various mitogen-activated protein kinases in cervical cancer cells

“…The increase of HeLa cell growth inhibition by the combination of RHL with U0126 was accompanied by the enhancement of the activation of caspase-3/7 and PARP, suggesting that ERK is involved in regulating cell survival. The finding that RHL inhibited ERK activation was shown in another study using human mammary epithelial MCF cells (9). However, in our study, the activation of ERK was increased following RHL treatment in HeLa cells.…”

“…Our previous study showed that RHL exhibits anti-cancer activity in breast and ovarian cancer, and hepatocellular carcinoma in vivo and in vitro (9)(10)(11). In the present study, RHL was shown to inhibit the growth of human cervical cancer cells.…”

“…Our previous study showed that rhein lysinate (RHL; the salt of rhein and lysine, easily dissolved in water) exhibits anti-cancer activity in breast and ovarian cancer and in hepatocellular carcinoma in vivo and in vitro (9)(10)(11).…”

Effects of Rhein Lysinate on H2O2-induced cellular senescence of human umbilical vascular endothelial cells

“…In previous studies, Rhein was found to have a variety of bioactivities, such as inhibiting IL-1 induced chondrocyte activation [9] , decreasing hypertrophy in mesangial cells [10] , inhibiting tumor cell proliferation, and inducing tumor cell apoptosis [11] . In our previous study, we also found that a dose of more than 20 µmol/L RHL could inhibit tumor cell proliferation, and it acted synergistically with Taxol when combined, both in vitro and in vivo [12] . However, less than 20 µmol/L RHL can also improve cell viability.…”

Potential Therapeutic Molecular Targets for Nasopharyngeal Carcinoma

“…The anti-angiogenic property of rhein has been characterized in a zebrafish model (97,98). Interestingly, rhein lysinate showed a synergistic increase in the anti-tumor activity of Taxol in mice (185,186). It has also been shown to influence cell growth and apoptosis in several human cancer cell lines such as cervical cancer Ca Ski (120), colon adenocarcinoma CaCo-2 (245), glioma U-373MG (74), hepatocellular carcinoma BEL-7402 (265), hepatoblastoma HepG2 (146), lung cancer A549 (108), promyelocytic leukemia HL-60 (181), and human tongue SSC-4 cancer cell lines (42,150).…”