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Penn State University

1. Charepalli, Venkata Rohit. POLYPHENOL-RICH FOODS AS INHIBITORS OF COLON CANCER STEM CELLS.

Degree: 2018, Penn State University

The role of cancer stem cells (CSCs) in the initiation, progression and relapse of cancerous tumors has been studied in the past few years. Epidemiological studies have revealed a causal association between consumption of a diet rich in fruits and vegetables with reduced risk of colon cancer. This is believed to be due in part to the presence of polyphenols such as anthocyanins, procyanidins and phenolic acid derivatives. However, the effect of these compounds on colon CSCs has not been studied. In the present studies, I investigated the effects of polyphenol-rich Eugenia jambolana (Java plum), resveratrol-grape seed extract (RSV-GSE) and purple-fleshed potatoes on colon CSCs. The overall goal of this project was to investigate the anti-cancer effect of these polyphenolic compounds and polyphenol-rich foods on colon CSCs in vitro and in vivo, and to explore the underlying mechanisms of action.
 Java plum is a tropical fruit rich in anthocyanins and is typically grown in Florida and Hawaii in the US. I characterized the anthocyanin profile of Java plum using HPLC-MS and found that Java plum anthocyanin extract (JPE) contains a variety of anthocyanins including glucosides of delphinidin, cyanidin, petunidin, peonidin and malvidin. To evaluate the anti-cancer effects JPE, I treated cancer cells and colon CSCs (positive for CD 44, CD 133 and ALDH1b1 markers), with JPE at 30 and 40 μg/mL for 24 hours. Cell viability was assessed using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay and enumeration of viable cells. I evaluated induction of apoptosis by JPE using the TUNEL and caspase 3/7 glo assays. JPE suppressed proliferation in HCT-116 cells by more than 50 % and elevated apoptosis in both HCT-116 cells (200 %) and colon CSCs (165 %). JPE also inhibited the colony formation ability in colon CSCs as evaluated using colony formation assay. These results warrant further investigation of the anti-colon cancer effects of java plum using animal models of colon cancer. We have previously shown that anthocyanin-containing baked purple-fleshed potato (PP) extracts suppressed early and advanced human colon cancer cell proliferation and induced apoptosis, but their effect on colon CSCs is not known. In my research, both colon CSCs with functioning p53 and those with shRNA-attenuated p53 were treated with 5.0 μg/mL baked PP extracts (PA) for 24 hours. Effects of PA were compared to positive control sulindac. Cell proliferation was assayed using BrdU incorporation and apoptosis was assayed using TUNEL assay. In vitro, PA suppressed proliferation and elevated apoptosis in a p53 independent manner in colon CSCs. To evaluate the pathways targeted by PA, after treatment protein fraction of the cells was extracted and western blotting was used to look at the levels of proteins in Wnt/β-catenin and mitochondrial apoptotic signaling pathways. PA, but not sulindac, suppressed levels of Wnt pathway effector β-catenin (a critical regulator of CSC proliferation) and its downstream proteins (c-Myc and… Advisors/Committee Members: Jairam Kp Vanamala, Dissertation Advisor/Co-Advisor, Jairam Kp Vanamala, Committee Chair/Co-Chair, Joshua D Lambert, Committee Member, Gregory Ray Ziegler, Committee Member, Mary J Kennett, Outside Member.

Subjects/Keywords: Cancer stem cells; polyphenols; purple-fleshed potatoes; cancer prevention; resveratrol; grape seed extract; β-catenin; colon cancer

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APA (6th Edition):

Charepalli, V. R. (2018). POLYPHENOL-RICH FOODS AS INHIBITORS OF COLON CANCER STEM CELLS. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/14912vxc166

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Charepalli, Venkata Rohit. “POLYPHENOL-RICH FOODS AS INHIBITORS OF COLON CANCER STEM CELLS.” 2018. Thesis, Penn State University. Accessed December 05, 2020. https://submit-etda.libraries.psu.edu/catalog/14912vxc166.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Charepalli, Venkata Rohit. “POLYPHENOL-RICH FOODS AS INHIBITORS OF COLON CANCER STEM CELLS.” 2018. Web. 05 Dec 2020.

Vancouver:

Charepalli VR. POLYPHENOL-RICH FOODS AS INHIBITORS OF COLON CANCER STEM CELLS. [Internet] [Thesis]. Penn State University; 2018. [cited 2020 Dec 05]. Available from: https://submit-etda.libraries.psu.edu/catalog/14912vxc166.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Charepalli VR. POLYPHENOL-RICH FOODS AS INHIBITORS OF COLON CANCER STEM CELLS. [Thesis]. Penn State University; 2018. Available from: https://submit-etda.libraries.psu.edu/catalog/14912vxc166

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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