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Enhancement of the Chemopreventive and Chemotherapeutic Effects of Genistein and Beta-lapachone in Human Prostate Cancer Cells by Pyroelectrically Generated Very Low Dose Ionizing Radiation

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Date Issued:
2015
Summary:
An estimated 220,800 new prostate cancer cases and 27,540 deaths are expected to occur in US men by the end of 2015. Despite the increased treatment modes for prostate cancer, there is still no definite cure, and prognosis remains, at best, cautiously optimistic. The explicit amalgamation of two or more cancer therapeutic modalities such as surgery, radiation, and chemotherapy, has been one of the main interests of clinical investigation for several decades. Genistein (GN) and Beta-lapachone (BL) are two of the most promising anticancer phytochemical compounds. However, the anticancer activities of BL have been correlated with the enzyme activity of NQO1. The aim of this study was to investigate the enhancing effects of VLDR derived from a portable pyroelectric crystal generator on the chemopreventive and/or chemotherapeutic effects of GN and BL in NQO1+ PC3 and NQO1± (deficient) LNCaP prostate cancer cells (PCa) in vitro. The combination treat ment-induced cytotoxicity was investigated via MTT and Trypan blue exclusion assays. Dicoumarol (an NQO1 inhibitor) was co-administered to assess the effect of VLDR on NQO1 modulation. Nitro-blue tetrazolium assay was used to assess the intracellular ROS levels. Fluorescence microscopy was also used to assess the mode of cell death. In this study, a novel quantitative modeling approach was employed to comparably assess the cytotoxic effects of specific drugs used alone or in combinations with VLDR and to predict the potential synergistic therapeutic combinations. The data suggests that VLDR induced a rise in ROS levels, followed by upregulation in NQO1 levels. Pharmacodynamic indices were developed to quantify and characterize the combination treatment as synergistic, additive or antagonistic per dose or time-interval. Synergism was found to be dose and time-interval dependent. The major mode of cell death by this combination therapeutic regimen was found to be via apoptosis . In conclusion, our results confirm that VLDR enhanced cytotoxicity effects of both drugs dose- and time-dependently.
Title: Enhancement of the Chemopreventive and Chemotherapeutic Effects of Genistein and Beta-lapachone in Human Prostate Cancer Cells by Pyroelectrically Generated Very Low Dose Ionizing Radiation.
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Name(s): Oseni, Saheed Oluwasina, author
Kumi-Diaka, James, Thesis advisor
Florida Atlantic University, Degree grantor
Charles E. Schmidt College of Science
Department of Biological Sciences
Type of Resource: text
Genre: Electronic Thesis Or Dissertation
Date Created: 2015
Date Issued: 2015
Publisher: Florida Atlantic University
Place of Publication: Boca Raton, Fla.
Physical Form: application/pdf
Extent: 120 p.
Language(s): English
Summary: An estimated 220,800 new prostate cancer cases and 27,540 deaths are expected to occur in US men by the end of 2015. Despite the increased treatment modes for prostate cancer, there is still no definite cure, and prognosis remains, at best, cautiously optimistic. The explicit amalgamation of two or more cancer therapeutic modalities such as surgery, radiation, and chemotherapy, has been one of the main interests of clinical investigation for several decades. Genistein (GN) and Beta-lapachone (BL) are two of the most promising anticancer phytochemical compounds. However, the anticancer activities of BL have been correlated with the enzyme activity of NQO1. The aim of this study was to investigate the enhancing effects of VLDR derived from a portable pyroelectric crystal generator on the chemopreventive and/or chemotherapeutic effects of GN and BL in NQO1+ PC3 and NQO1± (deficient) LNCaP prostate cancer cells (PCa) in vitro. The combination treat ment-induced cytotoxicity was investigated via MTT and Trypan blue exclusion assays. Dicoumarol (an NQO1 inhibitor) was co-administered to assess the effect of VLDR on NQO1 modulation. Nitro-blue tetrazolium assay was used to assess the intracellular ROS levels. Fluorescence microscopy was also used to assess the mode of cell death. In this study, a novel quantitative modeling approach was employed to comparably assess the cytotoxic effects of specific drugs used alone or in combinations with VLDR and to predict the potential synergistic therapeutic combinations. The data suggests that VLDR induced a rise in ROS levels, followed by upregulation in NQO1 levels. Pharmacodynamic indices were developed to quantify and characterize the combination treatment as synergistic, additive or antagonistic per dose or time-interval. Synergism was found to be dose and time-interval dependent. The major mode of cell death by this combination therapeutic regimen was found to be via apoptosis . In conclusion, our results confirm that VLDR enhanced cytotoxicity effects of both drugs dose- and time-dependently.
Identifier: FA00004530 (IID)
Degree granted: Thesis (M.S.)--Florida Atlantic University, 2015.
Collection: FAU Electronic Theses and Dissertations Collection
Note(s): Includes bibliography.
Subject(s): Apoptosis -- Molecular aspects
Genistein -- Therapeutic use
Phytochemicals -- Physiological effect
Phytochemicals -- Therapeutic use
Prostate -- Cancer -- Adjuvant treatment
Prostate -- Cancer -- Cryptopathology
Prostate -- Cancer -- Molecular aspects
Held by: Florida Atlantic University Libraries
Sublocation: Digital Library
Links: http://purl.flvc.org/fau/fd/FA00004530
Persistent Link to This Record: http://purl.flvc.org/fau/fd/FA00004530
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Host Institution: FAU
Is Part of Series: Florida Atlantic University Digital Library Collections.