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Unlocking the Phytotherapeutic Synergism between Beta-lapachone and Soybean-derived Genistein in Human Prostate cancer cells
Title
Unlocking the Phytotherapeutic Synergism between Beta-lapachone and Soybean-derived Genistein in Human Prostate cancer cells.
Creator
Oseni, Saheed Oluwasina, Sandoval-Bernal, Bibiana, Kumi-Diaka, James, Graduate College
Abstract/Description
Prostate cancer after many years is still the second most common cancer in American men with about 233,000 new cases and 29,480 deaths estimated to be occurring in 2014. Despite the wide spectra of reports demonstrating the anti-cancer phytotherapeutic potentials of beta-lapachone and soybean-derived genistein in various tumors, little emphasis had been placed on their synergistic effects in androgen-independent PC3 and androgen-dependent LNCaP prostate cancer cell lines. In this study, we...
Show moreProstate cancer after many years is still the second most common cancer in American men with about 233,000 new cases and 29,480 deaths estimated to be occurring in 2014. Despite the wide spectra of reports demonstrating the anti-cancer phytotherapeutic potentials of beta-lapachone and soybean-derived genistein in various tumors, little emphasis had been placed on their synergistic effects in androgen-independent PC3 and androgen-dependent LNCaP prostate cancer cell lines. In this study, we aim to characterize the combined effects of genistein and b-lapachone on the phyto/chemosensitivity of LNCaP and PC3 human prostate cancer cells in-vitro, using MTT assay and LDH assay to study treatment-induced growth inhibition and cytotoxicity. Annexin-V-FITC and PI-TUNEL assays were also used to determine the potential treatment-induced apoptosis and/or necrosis. Our results revealed that both PC3 and LNCaP are phytosensitive to both single and combined treatments, though time-and dose-dependent. We observed that our treatments induced dual death pathways-apoptosis and necrosis-in both cell types and also observed that growth inhibition in both correlated positively with cell death in which, b-lapachone and genistein induced cell cycle arrest at the G1 and/or S phase and G2–M checkpoints respectively. Invariably, our results indicate that combination treatments with b-lapachone and genistein are more potent in killing both PC3 and LNCaP cancer cells than treatment with either genistein or b-lapachone alone. Our current results are therefore in agreement with the hypothesis that drugcombinations that target cell cycles at different critical checkpoints are more effective in causing cell death.
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Date Issued
2014
PURL
http://purl.flvc.org/fau/fd/FA00005845
Format
Document (PDF)
Pyroelectric Crystal Generated Very Low Dose X-rays Enhanced the Phytotherapeutic Effects of Beta-lapachone in Hormone Dependent Prostate Cancer Cells In Vitro
Title
Pyroelectric Crystal Generated Very Low Dose X-rays Enhanced the Phytotherapeutic Effects of Beta-lapachone in Hormone Dependent Prostate Cancer Cells In Vitro.
Creator
Oseni, Saheed Oluwasina, Kumi-Diaka, James, Jebelli, Joubin, Graduate College, Goldsmith, Harris, Kaldas, George, Branly, Rolando
Abstract/Description
In 2015, an estimated 220, 800 new cases and 27, 540 deaths are expected to occur due to prostate cancer in US men, thus adding to the economic burden of the over 2.6 million men currently battling the disease. Plethora of studies have demonstrated the phytotherapeutic potentials of beta-lapachone, a phytochemical compound derived from the bark of the lapacho tree, native to South America. Betalapachone (β-lap) has been shown to exhibit its anti-cancer effects majorly by the futile cycling...
Show moreIn 2015, an estimated 220, 800 new cases and 27, 540 deaths are expected to occur due to prostate cancer in US men, thus adding to the economic burden of the over 2.6 million men currently battling the disease. Plethora of studies have demonstrated the phytotherapeutic potentials of beta-lapachone, a phytochemical compound derived from the bark of the lapacho tree, native to South America. Betalapachone (β-lap) has been shown to exhibit its anti-cancer effects majorly by the futile cycling between the oxidized and the two electron reduction of β-lap mediated by NAD(P)H:quinone oxidoreductase (NQO1) resulting in the generation of reactive oxygen species (ROS) using NADH or NAD(P) as electron sources. β-lap is known to selectively kill human cancer cells, since NQO1 is expressed more abundantly in numerous human solid tumors than in the adjacent normal tissues; NQO1 has been shown to be exceptionally under expressed in hormone dependent prostate cancer cells (LNCaP) compared to the hormone independent prostate cancer cells (PC3). This study was aimed to investigate the enhancing effects of very low dose radiation (VLDR (20mGy)) derived from a pyroelectric crystal generator on the phytotherapeutic activity of beta-lapachone in LNCaP cell line in vitro accessed by MTT and Trypan blue assay. Treatment-induced intracellular levels of ROS were also assessed using Nitro blue tetrazolium assay. NQO1 activities in LNCaP cells were also investigated following treatment with VLDR and/or β-lap using Dicoumarol (NQO1 inhibitor). Results indicate that LNCaP cells respond significantly to combined treatments compared to single treatments.
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Date Issued
2015
PURL
http://purl.flvc.org/fau/fd/FA00005905
Format
Document (PDF)
Chemopreventive Effects of Magnesium Chloride Supplementation on Hormone Independent Prostate Cancer Cells
Title
Chemopreventive Effects of Magnesium Chloride Supplementation on Hormone Independent Prostate Cancer Cells.
Creator
Saheed Oluwasina Oseni, Elsa Quiroz, James Kumi-Diaka
Abstract/Description
Lifestyle significantly impacts the risk factors associated with prostate cancer, out of which diet appears to be the most influential. An emerging chemopreventive approach, which involves the adequate intake of dietary constituents, has shown great potential in preventing the occurrence or progression of cancer. Magnesium is known to be an essential cofactor for more than 300 enzymatic processes, and is responsible for the regulation of various cellular reactions in the body. A plethora of...
Show moreLifestyle significantly impacts the risk factors associated with prostate cancer, out of which diet appears to be the most influential. An emerging chemopreventive approach, which involves the adequate intake of dietary constituents, has shown great potential in preventing the occurrence or progression of cancer. Magnesium is known to be an essential cofactor for more than 300 enzymatic processes, and is responsible for the regulation of various cellular reactions in the body. A plethora of studies have shown evidence that changes in the intracellular levels of magnesium could contribute to cell proliferation and apoptosis in some normal and malignant cells. The aim of the study was to investigate the effects of magnesium chloride (MgCl2) in DU-145 prostate cancer cells.
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Date Issued
2016
PURL
http://purl.flvc.org/fau/fd/FAUIR000486
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)
ROLE OF INTERLEUKIN-1 RECEPTOR-ASSOCIATED KINASES IN CHRONIC INFLAMMATION AND PROSTATE TUMORIGENESIS
Title
ROLE OF INTERLEUKIN-1 RECEPTOR-ASSOCIATED KINASES IN CHRONIC INFLAMMATION AND PROSTATE TUMORIGENESIS.
Creator
Oseni, Saheed Oluwasina, Kumi-Diaka, James, Florida Atlantic University, Department of Biological Sciences, Charles E. Schmidt College of Science
Abstract/Description
The oncogenic role of many of inflammatory genes in prostate cancer (PCa) remains unexplored despite the increasing association of chronic inflammation with PCa initiation, progression, and therapy resistance. The overarching goal of this project was to identify dysregulated inflammatory genes that correlate with PCa progression and seek to understand their molecular mechanisms and the therapeutic potential of targeting them. To achieve this, we utilized cutting-edge integrative (epi) genomic...
Show moreThe oncogenic role of many of inflammatory genes in prostate cancer (PCa) remains unexplored despite the increasing association of chronic inflammation with PCa initiation, progression, and therapy resistance. The overarching goal of this project was to identify dysregulated inflammatory genes that correlate with PCa progression and seek to understand their molecular mechanisms and the therapeutic potential of targeting them. To achieve this, we utilized cutting-edge integrative (epi) genomic and transcriptomic techniques to identify and characterize inflammatory genes whose deregulation or (epi) genetic alterations correlate with PCa progression. Weighted Gene Co-expression Network Analysis and other multivariate analysis techniques identified IRAK1 as one of the inflammatory signatures found to be overexpressed in over 80% of prostate adenocarcinoma (PRAD) samples. We also explored the diagnostic and prognostic potential of IRAK1 as a biomarker using Kaplan Meier Survival Analysis and AUROC Analysis. DNA methylation analysis showed that IRAK1 is hypomethylated and found to negatively correlate with its overexpression in PRAD patients. We also found some missense and truncated mutations in some patients and reported a high level of IRAK1 gene amplification in castration-resistant and neuroendocrine PCa patients.
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Date Issued
2021
PURL
http://purl.flvc.org/fau/fd/FA00013713
Subject Headings
Prostate--Cancer, Interleukin-1 Receptor-Associated Kinases, Inflammation
Format
Document (PDF)