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A study of the chemopreventive effects of black raspberry components in rat esophageal epithelial cells

Zikri, Nancy N.

Abstract Details

2008, Doctor of Philosophy, Ohio State University, Public Health.
Our laboratory has demonstrated the preventive effects of freeze-dried black raspberries 0028BRB0029 on tumor development in the rat esophagus and colon in vivo. In attempts to explain these inhibitory effects, we tested two BRB extracts and two component anthocyanins 0028cyanidin-3-O-glucoside and cyanidin-3-O-rutinoside0029 in BRB for their effects on growth, apoptosis and gene expression in weakly tumorigenic 0028RE-1490029 and highly tumorigenic 0028RE-149 DHD0029 rat esophageal cell lines. The ethanol 0028EtOH0029 extract 0028100 00B5g/ml0029 and both anthocyanins 002850 00B5g/ml0029 had a selective growth-inhibitory pattern similar to that of both extracts. The EtOH extract and cyanidin-3-O-rutinoside induced capsases 3 and 7 activities significantly in RE-149 DHD cells. The growth inhibitory and the pro-apoptotic effects were enhanced by the daily addition of the EtOH extract and the anthocyanins to the medium. Maximal uptake of the anthocyanins in the EtOH extract by RE-149 DHD cells occurred after 1 hour of extract treatment followed by a rapid loss of anthocyanins from the cells. The uptake of anthocyanins by RE-149 cells had the same pattern as RE-149 DHD cells, but the amount of anthocyanins taken up was 100 times lower. This finding might explain the difference in the inhibitory effect of EtOH extract in both cell lines. Using DNA microarray technique, the EtOH extract was found to down-regulate multiple genes associated with esophageal tumors. The calcium signaling pathway was a major pathway modulated by the extract since several genes were down-regulated and all of them are linked to calcium, and all are involved in tumor development and progression in several organ sites.These genes include: calmodulin kinase II 0028CaMKII0029, protein kinase C iota 0028PKC03B90029, MAPK 9, and Cdc 25 a and b. The EtOH extract was found to down-regulate 16 genes consistently including: SERCA2a which functions as a calcium pump, fibroblast growth factor receptor 2, insulin-like growth factor binding protein 5, secreted protein acidic and rich in cysteine 0028SPARC0029, and galanin, all of which were demonstrated to play crucial roles in tumor development in multiple organs including the esophagus.
Gary Stoner (Advisor)
174 p.

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Citations

  • Zikri, N. N. (2008). A study of the chemopreventive effects of black raspberry components in rat esophageal epithelial cells [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1198691632

    APA Style (7th edition)

  • Zikri, Nancy. A study of the chemopreventive effects of black raspberry components in rat esophageal epithelial cells. 2008. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1198691632.

    MLA Style (8th edition)

  • Zikri, Nancy. "A study of the chemopreventive effects of black raspberry components in rat esophageal epithelial cells." Doctoral dissertation, Ohio State University, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=osu1198691632

    Chicago Manual of Style (17th edition)