Effects of Monascus-fermented rice extract on malignant cell-associated neovascularization and intravasation determined using the chicken embryo chorioallantoic membrane model.
The traditional Chinese medicine, Hong-Qu, also called red mold rice in the United States and Europe, is used for treating blood stasis, a disorder related to hyperlipidemia and atherosclerosis. In addition to improving metabolic syndrome, extracts from Monascus-fermented rice inhibit the proliferation of various cancer cells in vitro and in vivo. The objective was to examine the effect of red mold rice ethanol extract (RMRE) on angiogenesis, invasion, and metastasis during tumor progression. RMRE significantly inhibited the proliferation of SW480 and SW620 human colorectal carcinoma cells in a dose- and time-dependent manner by using the MTT assay. A capillary-like network morphology was observed after the addition of 20 ng/mL vascular endothelial growth factor or SW620 culture-conditional medium, which was not seen after RMRE treatment. Moreover, spontaneous intravasation into Matrigel grafts of SW620 cells from the upper to the lower layers in the chick embryo chorioallantoic membrane (CAM) model was detected by the polymerase chain reaction (PCR) amplification of human Alu genomic DNA from the lower CAMs in the RMRE-untreated group. Neovascularization increased to 75.3% +/- 11.6% by SW620 cells onplant with Matrigel grafts in the CAM model. However, RMRE significantly reduced CAM neovascularization in a dose-dependent manner. Finally, RMRE effectively decreased the activity of matrix metalloproteinase (MMP)-7 as determined by reverse transcription PCR (RT-PCR), Western blotting, and casein zymography assays. In summary, Monascus-fermented products exert a potent effect on tumor growth and activation, suggesting that they may serve as supplementary agents in adjuvant cancer therapy.
Ho
Bing-Ying
BY
Institute of Microbiology and Biochemistry, College of Life Science, National Taiwan University, Taipei, Taiwan.
Wu
Yao-Ming
YM
Hsu
Ya-Wen
YW
Hsu
Li-Chuan
LC
Kuo
Yao-Haur
YH
Chang
King-Jen
KJ
Pan
Tzu-Ming
TM
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000187:drug effects / Q000473:pathology; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005285:Fermentation; D006801:Humans; D020783:Matrix Metalloproteinase 7 / Q000187:drug effects / Q000378:metabolism; D008516:Medicine, Chinese Traditional / Q000379:methods; D032741:Monascus / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D012275:Oryza / Q000737:chemistry*; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D010936:Plant Extracts; D020783:Matrix Metalloproteinase 7