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      Induction of Apoptosis in Human Breast Adenocarcinoma Cells MCF-7 by Monapurpyridine A, a New Azaphilone Derivative from Monascus purpureus NTU 568

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          Abstract

          A new azaphilonidal derivative, monapurpyridine A ( MPA), has recently been isolated from the fermented products of Monascus purpureus NTU 568. The structure of MPA was elucidated by nuclear magnetic resonance ( 1H-NMR, 13C-NMR, COSY, HMQC, and HMBC) and other spectroscopic analyses. Biological evaluation revealed that MPA could induce cell death in human breast adenocarcinoma cells MCF-7, and it has no significant toxicity to normal mammary epithelial cells M10. The MTT assay and flow cytometric analysis were employed to investigate cell viability and cell cycle influenced by MPA. Moreover, we used Western blot and caspase activity assay to demonstrate the activation of caspase-3, -8 and -9 resulted from MPA. All evidence supported that MPA was suitable for developing into a chemotherapeutic or chemopreventive agent against breast cancer.

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          Most cited references17

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          Effect of red mold rice on antifatigue and exercise-related changes in lipid peroxidation in endurance exercise.

          This study evaluated the effect of red mold rice supplementation on antifatigue and exercise-related changes in lipid peroxidation of male adult Wistar rats through swimming exercise. Thirty 16-week-old rats were studied by dividing them into three groups (ten for each group). Other than the control group (CD), the other two groups were divided into a high-dose (HD) treatment group (5 g red mold rice/kg body weight for the HD group), and a low-dose (LD) group (1 g red mold rice/kg body weight for the LD group). Swimming endurance tests were conducted after 28 days of red mold rice supplementation, and the result showed that the treatment group showed a higher exercise time (CD, 78.0+/-6.4; LD, 104.2+/-9.6; and HD, 129.4+/-10.9 min; p<0.05) and a higher blood glucose concentration (CD, 76.67+/-8.08; LD, 111.34+/-8.50; and HD, 117.67+/-11.06 mg/dl; p<0.05) than the CD. Moreover, the blood lactate (CD, 45.00+/-0.90; LD, 31.41+/-1.80; and HD, 28.89+/-1.62 mg/dl; p<0.05), blood urea nitrogen (CD, 21.87+/-0.75; LD, 20.33+/-0.83; and HD, 20.53+/-1.09 mg/dl; p<0.05), and hemoglobin (CD, 14.20+/-0.21; LD, 13.70+/-0.55; and HD, 13.28+/-0.35 g/dl; p<0.05) were also significantly lower than those of the CD. Besides, the result suggested that the red mold rice supplementation may decrease the contribution of exercise-induced oxidative stress and improve the physiological condition of the rats.
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            Ankaflavin from Monascus-fermented red rice exhibits selective cytotoxic effect and induces cell death on Hep G2 cells.

            Monascus-fermented red rice has traditionally been used as a natural food colorant or food preservative of meat and fish for centuries. Recently, it has become a popular dietary supplement due to many of its bioactive constituents being discovered. Commercial Monascus-fermented red rice was used in this study. According to the cell-based cytotoxicity assay, a compound with selective cytotoxicity was found and identified as ankaflavin. Ankaflavin was found to be toxic to human cancer cell lines Hep G2 and A549 with a similar IC50 value of 15 microg/mL, while it posed no significant toxicity to normal MRC-5 and WI-38 cells at the same concentration. For elucidating the possible mode of cell death, Hep G2 cells were treated with ankaflavin for 48 h to examine the morphological change of the chromatin. Chromosomal condensation and fragmentation were found, and a significant sub-G1 peak was found by flow cytometry. Apoptosis was therefore suggested as the possible mechanism. Monascin, an analogue of ankaflavin, was also tested in this study. However, it showed no cytotoxicity and did not induce death of Hep G2 cells.
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              Azaphilones, furanoisophthalides, and amino acids from the extracts of Monascus pilosus-fermented rice (red-mold rice) and their chemopreventive effects.

              Six azaphilones, monascin (1), ankaflavin (2), rubropunctatin (3), monascorburin (4), rubropunctamine (5), and monascorburamine (6), two furanoisophthalides, xanthomonasin A (7) and xanthomonasin B (8), and two amino acids, (+)-monascumic acid (9) and (-)-monascumic acid (10), isolated from the extracts of Monascus pilosus-fermented rice (red-mold rice) were evaluated for their inhibitory effects on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in mice, on the induction of Epstein-Barr virus early antigen (EBV-EA) by TPA in Raji cells, and on the activation of (+/-)-(E)-methyl-2[(E)-hydroxy-imino]-5-nitro-6-methoxy-3-hexemide (NOR 1), a nitric oxide (NO) donor. Among the compounds tested, seven compounds (1-6 and 10) on TPA-induced inflammation, and six compounds (1, 3-5, 9, and 10) on EBV-EA activation, exhibited potent inhibitory effects. All of the compounds tested showed moderate inhibitory effects on NOR 1 activation.
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                Author and article information

                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                11 January 2012
                January 2012
                : 17
                : 1
                : 664-673
                Affiliations
                [1 ]Department of Biochemical Science and Technology, National Taiwan University, Taipei 10617, Taiwan
                [2 ]Division of Herbal Drugs and Natural Products, National Research Institute of Chinese Medicine, Taipei 11221, Taiwan
                [3 ]Graduate Institute of Integrated Medicine, China Medical University, Taichung 40402, Taiwan
                Author notes
                [* ] Authors to whom correspondence should be addressed; Email: kuoyh@ 123456nricm.edu.tw (Y.-H.K.); tmpan@ 123456ntu.edu.tw (T.-M.P.); Tel.: +886-2-2820-1999 ext. 7061 (Y.-H.K.); Fax: +886-2-2823-6150 (Y.-H.K.); Tel.: +886-2-3366-4519 ext. 10 (T.-M.P.); Fax: +886-2-3366-3838 (T.-M.P.).
                Article
                molecules-17-00664
                10.3390/molecules17010664
                6268682
                22237681
                00ec9b5f-c63d-40a7-a336-095b0d7af210
                © 2012 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 21 November 2011
                : 06 January 2012
                : 06 January 2012
                Categories
                Article

                monascus purpureus ntu 568,azaphilone,monapurpyridine a,cytotoxicity,apoptosis

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