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.

• Authors: Ya-Jun Lin, Yong-Su Zhen
• Journal: Anti-cancer drugs (Anticancer Drugs) Vol. 20 Issue 1 Pg. 65-72 (Jan 2009) ISSN: 1473-5741 [Electronic] England
• PMID: 19343002 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anthraquinones
• EGFR protein, human
• ErbB Receptors
• Proto-Oncogene Proteins c-raf
• Extracellular Signal-Regulated MAP Kinases
• Mitogen-Activated Protein Kinase Kinases
• ras Proteins
• Lysine
• Paclitaxel
• rhein

Topics

• Animals
• Anthraquinones (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (pharmacology)
• Breast Neoplasms (drug therapy, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Dose-Response Relationship, Drug
• Drug Synergism
• ErbB Receptors (drug effects, metabolism)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Female
• Humans
• Inhibitory Concentration 50
• Lysine (administration & dosage)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Mitogen-Activated Protein Kinase Kinases (metabolism)
• Paclitaxel (administration & dosage)
• Phosphorylation
• Proto-Oncogene Proteins c-raf (metabolism)
• Signal Transduction (drug effects)
• Time Factors
• Xenograft Model Antitumor Assays
• ras Proteins (metabolism)