The roles of Monascus-fermented products on cancer chemopreventive and therapeutic modulation

• Main Authors: Bing-Ying Ho, 何秉穎
• Other Authors: Tzu-Ming Pan
• Format: Others
• Language: zh-TW
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/33893639373042872795

博士 === 國立臺灣大學 === 微生物與生化學研究所 === 98 === The Monascus fermented products are of special interest because of their use in the production of a range of oriental fermented foods. The secondary metabolites of Monascus in the modern research were confirmed had the suppression tumor metastasis, anti-inflammation, the suppression cholesterol production and so on many functions. Therefore, Monascus metabolites extremely suit to utilize cancer therapy to suppress the tumor metastasis and the inflammation responded. The first section described the effects of red mold rice on Lewis lung carcinoma (LLC) bearing in syngeneic C57BL/6 mice. Oral administration of 2% red mold rice and implant 5 × 105 LLC cells in mice for 14 days significantly inhibited the tumor progress (51.1%). In vitro assays, the investigation involved the effects of red mold rice ethanol extract (RMRE) on LLC cells invasion and metastasis. RMRE interference on Interleukin-6 (IL-6) induced cell invasion and metastasis gene expressions of matrix metalloproteinases (MMPs) contained MMP-2 and MMP-9. Moreover, the assessment of chemotherapeutic efficiency combined clinical drugs used on tumor cell viabilities have showed that RMRE not only significantly arrested LLC cells G1 phase, but also induced cell apoptosis following arise the doses of RMRE treatment. The secondary part represented that oral administration with RMRE or dramatically inhibited the metastatic ability of LLC-bearing mice caused by the decline of serum vascular endothelial growth factor (VEGF) levels compared with untreated metastatic groups. These results indicated that MK was a key antimetastatic and antiangiogenesis compound in RMRE and proved that by Matrigel-coating transwell and tube-forming assays, as well as reverse transcription polymerase chain reaction (RT-PCR) illustrated the downregulation of VEGF-stimulated invasive activity in LLC cells. The third section showed RMRE and DMA significantly inhibited the proliferation of SW480 and SW620 human colorectal carcinoma cells in dose- and time-dependent manner. Moreover, SW620 cells could growth in Matrigel grafts and spontaneously intravasation from the upper to the lower of chick embryo chorioallantoic membrane (CAM) model, which detected human Alu genomic DNA by PCR amplification from the lower CAMs at RMRE-untreated group. The percentage of neovascularization was increased 75.3±11.6% by SW620 cells onplant with Matrigel grafts on the CAM model. However, addition of RMRE significantly reduced CAM neovascularization in dose-dependent effect. Finally, we have finding that RMRE and DMA effectively decreased activity of MMP-7 determined by RT-PCR, Western blotting, and casein zymography assays. In summary, using the food-based approach to cancer prevention has shown that Monascus-fermented products ingestion inhibited both the primary tumor growth and metastatic progression on both LLC-bearing mice and chick embryo CAM models in vivo. Therefore, application of RMRE, MK, AK and DMA may serve as a non-toxic natural chemopreventive or antineoplastic agent for further development of cancer adjuvant chemotherapy. We conclude that Monascus is a highly potential herb for cancer therapy especially in tumor chemotherapy, the more appropriate application worthy to be studied in the future.