• Biomolecules & Therapeutics
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• v.17 no.4
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• pp.403-411
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• 2009

Thiacremonone, the main component isolated from heated garlic (Allium sativum L.), is interested for using as a cancer preventive or therapeutic agent since garlic has been known to be useful plant in the treatment of cancers. Nuclear factor kappaB (NF-${\kappa}B$) is constitutively activated in the prostate cancer and activation of NF-${\kappa}B$ is implicated in drug resistance in cancer cells. Docetaxel, a semisynthetic analog of paclitaxel, is an antineoplastic drug widely used for advanced various cancer. In previous studies, we found that thiacremonone inhibited activation of NF-${\kappa}B$ in cancer cells and marcrophages. In the present study, we investigated whether thiacremonone could increase susceptibility of prostate cancer cells (PC-3 and DU145) to docetaxel via inactivation of NF-${\kappa}B$. We found that the combination treatment of thiacremonone (50 ${\mu}g$/ml) with docetaxel (5 nM) was more effective in the inhibition of prostate cancer cell growth and induction of apoptosis accompanied with the significant inhibition of NF-${\kappa}B$ activity than those by the treatment of thiacremonone or docetaxel alone. It was also found that NF-${\kappa}B$ target gene expression of Bax, caspase-3 and caspase-9 was much more significantly enhanced, but the expression of Bcl-2 was also much more significantly inhibited by the combination treatment. These results indicate that thiacremonone inhibits NF-${\kappa}B$, and enhances the susceptibility of prostate cancer cells to docetaxel. Thus, thiacremonone could be useful as an adjuvant anti-cancer agent.

• BMB Reports
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• v.38 no.6
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• pp.639-645
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• 2005

Protein kinase C (PKC) isozymes, a family of serine-threonine kinases, are important regulators of cell proliferation and malignant transformation. Phorbol esters, the prototype PKC activators, cause PKC translocation to the plasma membrane in prostate cancer cells, and trigger an apoptotic response. Studies in recent years have determined that each member of the PKC family exerts different effects on apoptotic or survival pathways. $PKC{\delta}$, one of the novel PKCs, is a key player of the apoptotic response via the activation of the p38 MAPK pathway. Studies using RNAi revealed that depletion of $PKC{\delta}$ totally abolishes the apoptotic effect of the phorbol ester PMA. Activation of the classical $PKC{\alpha}$ promotes the dephosphorylation and inactivation of the survival kinase Akt. Studies have assigned a pro-survival role to $PKC{\varepsilon}$, but the function of this PKC isozyme remains controversial. Recently, it has been determined that the PKC apoptotic effect in androgen-dependent prostate cancer cells is mediated by the autocrine secretion of death factors. $PKC{\delta}$ stimulates the release of $TNF{\alpha}$ from the plasma membrane, and blockade of $TNF{\alpha}$ secretion or $TNF{\alpha}$ receptors abrogates the apoptotic response of PMA. Molecular analysis indicates the requirement of the extrinsic apoptotic cascade via the activation of death receptors and caspase-8. Dissecting the pathways downstream of PKC isozymes represents a major challenge to understanding the molecular basis of phorbol ester-induced apoptosis.

• Journal of Life Science
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• v.18 no.8
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• pp.1042-1048
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• 2008

Prostate cancer is the most predominant cancer in men and related death rate increases every year. Till date, there is no effective therapy for androgen independent prostate cancer. To investigate the mechanism for cell growth inhibition or apoptosis in human androgen independent prostate cancer PC-3 cells after gamma irradiation. The aim of this study was to examine the potential of gamma irradiation to induce apoptosis in PC-3 cells and to assess the mechanism of gamma irradiation-induced apoptosis. Five different assays were employed in this study: cell proliferation assay, morphological assessments of apoptotic cells, DNA fragmentation analysis, quantification of apoptosis by annexin V (AV) and propidium iodide (PI) staning, and western blot analysis. Cell viability was inversely related to radiation dose. DAPI-positive cells were detected 48 hr after 40 Gy radiation exposure. And nuclear morphological changes of cells were observed by gamma irradiation. DNA ladder patterns in the cells exposed to gamma-radiation were appeared at 24 hr. Also, gamma irradiation induces apoptosis of PC-3 cells via Caspase3, Bax and PARP-dependent fashion.

• Journal of Microbiology and Biotechnology
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• v.31 no.6
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• pp.775-783
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• 2021

Sea cucumber, Holothuria scabra, is a well-known traditional Asian medicine that has been used for suppressing inflammation, promoting wound healing, and improving immunity. Moreover, previous studies demonstrated that the extract from H. scabra contains many bioactive compounds with potent inhibitory effect on tumor cell survival and progression. However, the effect of the methanolic extract from the body wall of H. scabra (BWMT) on human prostate cancer cells has not yet been investigated. In this study, we aimed to investigate the effects and underlying mechanism of BWMT on prostate cancer cell viability and metastasis. BWMT was obtained by maceration with methanol. The effect of BWMT on cell viability was assessed by MTT and colony formation assays. The intracellular ROS accumulation was evaluated using a DCFH-DA fluorescence probe. Hoechst 33342 staining and Annexin V-FITC/PI staining were used to examine the apoptotic-inducing effect of the extract. A transwell migration assay was performed to determine the anti-metastasis effect. BWMT significantly reduced cell viability and triggered cellular apoptosis by accumulating intracellular ROS resulting in the upregulation of JNK and p38 signaling pathways. In addition, BWMT also inhibited the invasion of PC3 cells by downregulating MMP-2/-9 expression via the ERK pathway. Consequently, our study provides BWMT from H. scabra as a putative therapeutic agent that could be applicable against prostate cancer progression.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.1827-1831
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• 2015

Background: We generated a mouse model of prostate cancer based on the adult-prostate-specific inactivation of phosphatase and tensin homolog (PTEN) using the Cre-loxP system. The potential of our mice as a useful animal model was examined by evaluating the chemopreventive efficacy of the anti-androgen, chlormadinone acetate (CMA). Materials and Methods: Six-week-old mice were treated subcutaneously with $50{\mu}g/g$ of CMA three times a week for 9 or 14 weeks and sacrificed at weeks 15 and 20. Macroscopic change of the entire genitourinary tract (GUT) and histologically evident prostate gland tumor development were evaluated. Proliferation and apoptosis status in the prostate were examined by immunohistochemistry. Results: CMA triggered significant shrinkage of not only the GUT but also prostate glands at 15 weeks compared to the control (p=0.017 and p=0.010, respectively), and the trend became more marked after a further five-weeks of treatment. The onset of prostate adenocarcinoma was not prevented but the proliferation of cancer cells was inhibited by CMA, which suggested the androgen axis is critical for cancer growth in these mice. Conclusions: Conditional PTEN-deficient mice are useful as a preclinical model for chemoprevention studies and serve as a valuable tool for the future screening of potential chemopreventive agents.

• Toxicological Research
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• v.26 no.2
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• pp.109-115
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• 2010

The purpose of this study was to elucidate the mechanism underlying enhanced radiosensitivity to $^{60}Co\;{\gamma}$-irradiation in human prostate PC-3 cells pretreated with berberine. The cytotoxic effect of the combination of berberine and irradiation was superior to that of berberine or irradiation alone. Cell death and Apoptosis increased significantly with the combination of berberine and irradiation. Additionally, ROS generation was elevated by berberine with or without irradiation. The antioxidant NAC inhibited berberine and radiation-induced cell death. Bax, caspase-3, p53, p38, and JNK activation increased, but activation of Bcl-2, ERK, and HO-1 decreased with berberine treatment with or without irradiation. Berberine inhibited the anti-apoptotic signal pathway involving the activation of the HO-1/NF-${\kappa}B$-mediated survival pathway, which prevents radiation-induced cell death. Our data demonstrate that berberine inhibited the radioresistant effects and enhanced the radiosensitivity effects in human prostate cancer cells via the MAPK/caspase-3 and ROS pathways.

• Nutrition Research and Practice
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• v.15 no.1
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• pp.12-25
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• 2021

BACKGROUND/OBJECTIVES: The study was conducted to investigate the efficacy of the combination treatment of phytochemical resveratrol and the anticancer drug docetaxel (DTX) on prostate carcinoma LNCaP cells, including factors related to detailed cell death mechanisms. MATERIALS/METHODS: Using 2-dimensional monolayer and 3-dimensional spheroid culture systems, we examined the effects of resveratrol and DTX on cell viability, reactive oxygen species (ROS) levels, mitochondrial membrane potential, apoptosis, and necroptosis by MTT, flow cytometry, and Western blotting. RESULTS: At concentrations not toxic to normal human prostate epithelial cells, resveratrol effectively decreased the viability of LNCaP cells depending on concentration and time. The combination treatment of resveratrol and DTX exhibited synergistic inhibitory effects on cell growth, demonstrated by an increase in the sub-G0/G1 peak, Annexin V-phycoerythrin positive cell fraction, ROS, mitochondrial dysfunction, and DNA damage response as well as concurrent activation of apoptosis and necroptosis. Apoptosis and necroptosis were rescued by pretreatment with ROS scavenger N-acetylcysteine. CONCLUSIONS: We report resveratrol as an adjuvant drug candidate for improving the outcome of treatment in DTX therapy. Although the underlying mechanisms of necroptosis should be investigated comprehensively, targeting apoptosis and necroptosis simultaneously in the treatment of cancer can be a useful strategy for the development of promising drug candidates.

• Journal of Plant Biotechnology
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• v.48 no.2
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• pp.106-114
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• 2021

We evaluated the anti-cancer activity against human prostate cancer cells and the associated molecular mechanism of extracts from the branches of Rhamnus yoshinoi (RYB). Treatment with RYB suppressed viability of human prostate cancer cells (PC-3) and decreased protein levels of both β-catenin and T-cell factor 4 (TCF4). This was reflected in reduced TCF4 mRNA, but not decreased β-catenin mRNA. PC-3 cells were pretreated with the proteosome inhibitor MG132 before treatment with RYB, which blocked RYB-mediated down regulation of β-catenin in PC-3 cells, thus confirming that RYB promotes the proteasomal degradation of β-catenin. RYB induced β-catenin phosphorylation, and GSK-3β inhibition by LiCl blocked the phosphorylation and proteasomal degradation of β-catenin by RYB. These results suggest that GSK-3β may be an important upstream kinase for RYB-mediated regulation of β-catenin. Finally, GC/MS analysis of RYB identified 18 compounds. Based on these findings, RYB shows potential for development as a therapeutic agent for prostate cancer.

• The Korea Journal of Herbology
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• v.27 no.4
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• pp.17-23
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• 2012

Objectives : Schisandrae Fructus (SF) has traditionally been used to balance level of body fluid and to strengthen kidney function. It has been reported that the SF extract has antioxidant, hepatoprotective, neuroprotective and anticancer effects. This study investigated an antiproliferative effect of SF extract on PC-3 human prostate cancer cells and analyzed active ingredients of SF extract qualitatively and quantitatively. Methods : We examined the antiproliferative effect of SF extract with MTT assay, DAPI staining and annexin-V/7-AAD double staining. The active ingredients of SF extract were identified by using HPTLC and HPLC/DAD system. Results : SF-chloroform fraction inhibited growth of PC-3 cells and changed the morphology of nucleus in a dose dependent manner. A dose-dependent apoptotic cell death was also measured by flow cytometry analysis. It was analyzed that SF-chloroform fraction contained more schizandrin than other fractions by using HPTLC and HPLC/DAD system. Conclusions : These results suggest that SF extract and schizandrin may be a potential chemotherapeutic agent for the control of PC-3 human prostate cancer cells.

• Mass Spectrometry Letters
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• v.11 no.3
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• pp.52-58
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• 2020

Histidine phosphorylation (pHis) is increasingly recognized as an important post translational modification (PTM) in regulating cellular functions in eukaryotes. In order to clarify the role of pHis in mammalian cell signaling system, a global phosphorylation study was performed in human prostate cancer cells, PC-3M, using a TiO₂ affinity chromatography. A total number of 307 pHis sites were identified on the 268 proteins among total identified 9,924 phosphorylation sites on 3,316 proteins. In addition, 22 pHis proteins were classified in enzyme category. This report provides the first database for the study of pHis in prostate cancer cells.