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Potential mechanism of phytochemical-induced apoptosis in human prostate cancer cells: Genistein and beta-lapachone
Title
Potential mechanism of phytochemical-induced apoptosis in human prostate cancer cells: Genistein and beta-lapachone.
Creator
Saddler, Shawnette Simone, Florida Atlantic University, Kumi-Diaka, James
Abstract/Description
The present study was undertaken to determine the chemotherapeutic potential of genistein and beta-lapachone and possible mechanisms of action in prostate cancer in vitro. The bioassays used included: MTT and LDH chemosensitivity-cytotoxicity assays, NQO1 detection, annexin V-FITC, TUNEL and the caspase protease (CPP32) apoptotic detection assays. The results showed that: (i) PC3 cells are sensitive to single and combination treatments in a dose and time dependent manner; (ii) there was...
Show moreThe present study was undertaken to determine the chemotherapeutic potential of genistein and beta-lapachone and possible mechanisms of action in prostate cancer in vitro. The bioassays used included: MTT and LDH chemosensitivity-cytotoxicity assays, NQO1 detection, annexin V-FITC, TUNEL and the caspase protease (CPP32) apoptotic detection assays. The results showed that: (i) PC3 cells are sensitive to single and combination treatments in a dose and time dependent manner; (ii) there was treatment-induced dual death pathways (apoptosis and necrosis) with increasing toxicity (necrosis) at higher concentrations in single and combination treatments; (iii) combination treatment was more growth inhibitory than single treatments; (iv) the NQO1 enzyme substantially enhances the toxicity of beta-lapachone but not genistein, while genistein exerted its apoptotic inducing effects via the caspase 3 pathway. The overall results indicate that combination treatments with beta-lapachone and genistein are more efficacious in killing PC3 human prostate cancer cells than treatment with either agent alone.
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Date Issued
2003
PURL
http://purl.flvc.org/fcla/dt/13042
Subject Headings
Prostate--Cancer--Cytopathology, Apoptosis, Prostate--Cancer--Molecular aspects
Format
Document (PDF)
Anticancer activity of two dietary phytochemicals: Genistein and beta-lapachone
Title
Anticancer activity of two dietary phytochemicals: Genistein and beta-lapachone.
Creator
Merchant, Kendra T., Florida Atlantic University, Kumi-Diaka, James
Abstract/Description
Phytochemicals are biologically active secondary plant metabolites that have been shown to exhibit anti-cancer activity. The dietary phytochemicals genistein isoflavone and beta-lapachone, were investigated to determine their effect on the growth of human prostate adenocarcinoma cells in vitro. The cells were exposed to varying concentrations of both phytochemicals in single and combination treatments for specified time periods and their effect was determined using post-treatment cell...
Show morePhytochemicals are biologically active secondary plant metabolites that have been shown to exhibit anti-cancer activity. The dietary phytochemicals genistein isoflavone and beta-lapachone, were investigated to determine their effect on the growth of human prostate adenocarcinoma cells in vitro. The cells were exposed to varying concentrations of both phytochemicals in single and combination treatments for specified time periods and their effect was determined using post-treatment cell viability, treatment-induced apoptosis and cell signaling assays. The overall results revealed that both phytochemicals inhibited cell growth and proliferation and induced apoptosis in a dose-dependent manner for both single and combination treatments. However, combination treatments were not significantly more effective than single treatment with either drug. Both phytochemicals could therefore offer therapeutic efficacy in human prostate adenocarcinoma.
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Date Issued
2005
PURL
http://purl.flvc.org/fcla/dt/13250
Subject Headings
Phytochemicals--Physiological effect, Prostate--Cancer--Molecular aspects, Apoptosis--Molecular aspects, Prostate--Cancer--Treatment
Format
Document (PDF)
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
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.
Creator
Oseni, Saheed Oluwasina, Kumi-Diaka, James, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description
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 ...
Show moreAn 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.
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Date Issued
2015
PURL
http://purl.flvc.org/fau/fd/FA00004530, http://purl.flvc.org/fau/fd/FA00004530
Subject Headings
Apoptosis -- Molecular aspects, Genistein -- Therapeutic use, Phytochemicals -- Physiological effect, Phytochemicals -- Therapeutic use, Prostate -- Cancer -- Adjuvant treatment, Prostate -- Cancer -- Cryptopathology, Prostate -- Cancer -- Molecular aspects
Format
Document (PDF)
Impact of Vitamin C on Genistein-Induced Apoptosis in Prostate Cancer
Title
Impact of Vitamin C on Genistein-Induced Apoptosis in Prostate Cancer.
Creator
Famuyiwa, Toluleke, Kumi-Diaka, James, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description
This study determined the impact of vitamin C dose on genistein-induced apoptosis in LNCaP cancer cells at various treatment regimens in vitro. Although the linear regression of viability assay (MTT) indicated a p-value = 0.11; NBT assay reveal a declining SOD activity during cell death. Apoptosis induction was the main mode of treatment induced cell death. The overall data showed the trend of treatment efficacy as;(Gen 10uM + Vit C 40uM) > (Gen 30uM + Vit C 40uM) > (Gen 70uM + Vit C 40uM) >...
Show moreThis study determined the impact of vitamin C dose on genistein-induced apoptosis in LNCaP cancer cells at various treatment regimens in vitro. Although the linear regression of viability assay (MTT) indicated a p-value = 0.11; NBT assay reveal a declining SOD activity during cell death. Apoptosis induction was the main mode of treatment induced cell death. The overall data showed the trend of treatment efficacy as;(Gen 10uM + Vit C 40uM) > (Gen 30uM + Vit C 40uM) > (Gen 70uM + Vit C 40uM) > 10uM genistein > 70uM genistein. The chi-square test for comparing necrosis, apoptosis and life cells showed that Vitamin C could impact genistein-induced apoptosis in LNCaP cells (p = 0.0003). This study forms the basis for in vivo studies of the impact of vitamin C on genistein-induced apoptosis in LNCaP prostate cancer cells.
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Date Issued
2015
PURL
http://purl.flvc.org/fau/fd/FA00004497, http://purl.flvc.org/fau/fd/FA00004497
Subject Headings
Apoptosis -- Molecular aspects, Cellular signal transduction, Genistein -- Therapeutic use, Phytochemicals -- Physiological effect, Phytochemicals -- Therapeutic use, Prostate -- Cancer -- Adjuvant treatment, Prostate -- Cancer -- Molecular aspects, Vitamin C -- Therapeutic use
Format
Document (PDF)