• 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.

• Toxicological Research
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• v.18 no.1
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• pp.59-64
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• 2002

Substantial evidences have been accumulated about the hormone-like effects of exogenous substances such as pesticides and industrial chemicals during past years. The effects of these substances on the endocrine system are believed to be either enhancing or reducing of various endocrine action. It is necessary to identify putative causal agents by the batter system and to assess their ability to disrupt the endocrine system. A variety of in vitro and In vivo approaches have been used to determine the androgenic effects of environmental chemicals. To establish the method for assessment of the putative endocrine disruptors with androgenic activity, we carried out the cell proliferation assay by MTS method after treatment with the various concentration of testosterone in LNCaP cells (human prostatic cancer cell line) and also observed the expression of androgen-related genes by quantitative RT-PCR. In the cell proliferation assay, the results showed that the grouth of LNCaP cells increased within level of at least 10pM testosterone. We measured by quantitative RT-PCR method on the effects of testosterone on mRNA expression of androgen receptor (AR), prostate-specific antigen (PSA), bone morphogenetic protein (BMP) and BMP receptor (BMPR) In LNCaP cells. The results demonstrated that mRNA expression of PSA and BMPR-IB was observed differently within level of at least 0.01 pM testosterone compared with non-treated control. These observations suggest that the detection of PSA and BMPR-IB mRNA by the quantitative RT-PCR in LNCaP cells is very sensitive method to identify the endocrine disruptors to have the androgenic effects.

• Journal of the Korean Society of Food Science and Nutrition
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• v.37 no.1
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• pp.8-15
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• 2008

Saussurea lappa (SL) has been used to reduce abdominal pain and tenesmus in traditional oriental medicine. SL and major compounds of SL, sesquiterpene lactones, have been suggested to possess various biological effects, including anti-tumor, anti-ulcer, anti-inflammatory, anti-viral and cardiotonic activities. Recently, it has been reported that ethanol extracts from roots of SL have antiproliferative effects on gastric cancer cells. To explore the possibility that SL has chemopreventive effects on prostate cancer, we examined whether the hexane extract of SL (HESL) inhibits the growth of LNCaP human prostate cancer cells. Cells were incubated with various concentrations ($0{\sim}4$ mg/L) of HESL in DMEM/F12 containing 5% charcoal stripped fetal bovine serum. HESL substantially decreased viable cell numbers and induced apoptosis of LNCaP cells in dose-dependent manners. HESL increased the levels of cleaved caspase-8, -9, -7 and -3, and poly (ADP-ribose) polymerase. HESL increased the levels of the pro-apoptotic Bak and truncated-Bid proteins whereas it had no effect on the anti-apoptotic Bcl-2, Bcl-xL, or Mcl-1. The present results indicate that HESL inhibits the growth of human prostate cancer cells by inducing apoptosis, which involves the activation of the caspase cascades.

• Applied Microscopy
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• v.38 no.3
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• pp.245-250
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• 2008

Etoposide (Eto) is chemotherapeutic compounds that is currently used in the treatment of metastatic prostate cancer but new therapeutic agents are needed for the treatment of androgen-independent prostate cancer. The objective of the present study was to determine whether vitamin C (VC), the antioxidant, plays a role in regulating the growth of prostate cancer cell lines and whether VC has synergistic effect to tumor cell killing by chemotherapeutic drugs. Androgen-dependent LNCaP and androgen-independent DU-145 prostate cancer cell lines were used in this study. Both cells presented increase of dose- and time-dependent cytotoxicity in Eto-treated cultures. The combined treatment with Eto and VC significantly increased the percentage of apoptotic cells compared to Eto-treated cells(p<0.05). The present findings demonstrated that VC inhibited the growth of prostate cancer cell lines by Eto-mediated cytotoxicity and induced apoptosis. These results suggest that the chemotherapeutic effect of Eto on prostate cancer can be enhanced by VC.

• The Journal of Pediatrics of Korean Medicine
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• v.27 no.1
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• pp.59-68
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• 2013

Objectives The aim of this study is to investigate whether hwang-ryun-haedok-tang (HDT) affect proliferations of androgen-dependent LNCaP prostate cancer cells, androgen-independent PC-3, DU-145 prostate cancer cells, MCF-7 human breast cancer cells, A549, NCI-H292 human pulmonary cancer cells and K-562 human chronic myelogenous leukemia cells. Materials and Methods Effects of HDT on proliferations of each cancer cell line were investigated. 20,000 cells/well were plated in each well of 96-well culture plate. After 24 hrs, 0.01-10% of HDT in culture medium was added to cancer cells. The number of cells was counted by using SRB assay or direct cell counting method after 72 hours from drug treatment. Effect of baicalein or berebrine on proliferation was assessed according to the same method. Results (1) HDT inhibited proliferations of LNCaP, PC-3 and DU-145 prostate cancer cells. (2) HDT inhibited proliferation of MCF-7 breast cancer cells. (3) HDT also inhibited proliferations of A549, NCI-H292 pulmonary cancer cells and K-562 chronic myelogenous leukemia cells. (4) Baicalein and berberine also showed inhibitory effects on proliferations of prostate and breast cancer cells. Conclusion : HDT inhibited proliferations of human prostate, breast, pulmonary and blood cancer cells. These results suggest us the potential use of HDT as a chemopreventive or chemotherapeutic agent. Effect of HDT on human cancer should be further investigated using in vivo experimental models that can reflect pathophysiology of human cancer through another studies.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.4
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• pp.507-515
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• 2014

Benign prostatic hyperplasia (BPH), which is commonly found in aging men, is characterized by hyperplasia of prostatic stromal and epithelial cells beginning in the periurethral zone of the prostate. The prevalence of BPH increases in an age-dependent manner. Here, we investigated the protective effects of unripe Rubus occidentalis extracts (UROE) on BPH development using a prostate cancer cell line and testosterone-induced BPH rat model. Experiments using an established hormone-dependent prostate cancer cell line (LNCaP) showed that UROE treatment significantly decreased expression of androgen-related genes, including androgen receptor (AR), prostate specific antigen (PSA), and 5-alpha reductase 2, but not 5-alpha reductase 1, which was also observed in flutamide-treated cells. Further, AR and PSA gene expression was reduced by UROE treatment under androgen-stimulated conditions using dihydrotestosterone (DHT). BPH animals displayed elevated prostate weights. However, UROE as well as finasteride treatment significantly reduced prostate weights and DHT levels compared to testosterone-induced BPH animals. Histopathological analysis also showed that UROE treatment suppressed testosterone-induced prostatic hyperplasia. Taken together, the results suggest that UROE may effectively inhibit the development of BPH and thus may be a useful agent in BPH treatment.

• Journal of Mushroom
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• v.13 no.3
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• pp.181-184
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• 2015

Mushroom have long been valued as highly nutritious and tasty foods in many societies throughout the world. It is known for biological activities including anti-inflammatory and anti-oxidative potential. However little is known about anti-cancer property. In this study, we investigated the anti-prostate cancer activity of mushrooms. For that, eight kinds of mushrooms such as, T. matsutake, S. crispa, G. lucidum-US, G. lucidum-AS, C. cardinalis-BR, G. frondosa, P. linteus, U. esculenta were extracted with hot water. Among them, three kinds of mushrooms including T. matsutake, G. lucidum-US and C. militaris-BR extracts inhibited prostate specific antigen (PSA) expression in prostate cancer cell, LNCaP. These results demonstrate that some of mushrooms inhibited PSA expression suggesting that the mushrooms might be a candidate for the treatment of prostate cancer.

• International Journal of Industrial Entomology and Biomaterials
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• v.47 no.2
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• pp.140-146
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• 2023

In recent years, the number of patients with benign prostatic hyperplasia (BPH), a condition that commonly occurs in elderly men, has increased due to aging and the adoption of western dietary habits. Treatment with chemical drugs, such as finasteride or dutasteride, can cause side effects such as erectile dysfunction or sexual problems. This necessitates the development of remedies using natural substances derived from food ingredients. In this study, we investigated the inhibitory effects of Oxya chinensis sinuosa hot water extract (OCH) on BPH production in LNCaP cells, a hormone-dependent prostate cancer cell line. We found that the mRNA expression of androgen receptor (AR), prostate specific antigen (PSA), and, 5α-reductases 1, and 2 decreased following treatment with OCH. Furthermore, OCH treatment resulted in reduced protein expression of BPH regulators, such as AR. Collectively, these results suggest that OCH exerts a beneficial effect on BPH by inhibiting the AR signaling pathway, indicating the potential of OCH as a therapeutic agent for the prevention and treatment of BPH.

• BMB Reports
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• v.48 no.10
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• pp.559-564
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• 2015

We investigated the effects of mangiferin on the expression and activity of metalloproteinase (MMP)-9 and the invasion of tumor necrosis factor (TNF)-$\alpha$-stimulated human LNCaP prostate carcinoma cells. Reverse-transcription polymerase chain reaction (RT-PCR) and western blot analysis showed that mangiferin significantly reversed TNF-$\alpha$-induced mRNA and protein expression of MMP-9 expression. Zymography data confirmed that stimulation of cells with TNF-$\alpha$ significantly increased MMP-9 activity. However, mangiferin substantially reduced the TNF-$\alpha$-induced activity of MMP-9. Additionally, a matrigel invasion assay showed that mangiferin significantly reduced TNF-$\alpha$-induced invasion of LNCaP cells. Compared to untreated controls, TNF-$\alpha$-stimulated LNCaP cells showed a significant increase in nuclear factor-${\kappa}B$ (NF-${\kappa}B$) luciferase activity. However, mangiferin treatment markedly decreased TNF-$\alpha$-induced NF-${\kappa}B$ luciferase activity. Furthermore, mangiferin suppressed nuclear translocation of the NF-${\kappa}B$ subunits p65 and p50. Collectively, our results indicate that mangiferin is a potential anti-invasive agent that acts by suppressing NF-${\kappa}B$-mediated MMP-9 expression.

• BMB Reports
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• v.54 no.2
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• pp.130-135
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• 2021

Voltage-gated potassium (Kv) channels are involved in many important cellular functions and play pivotal roles in cancer progression. The expression level of Kv2.1 was observed to be higher in the highly metastatic prostate cancer cells (PC-3), specifically in their membrane, than in immortalized prostate cells (WPMY-1 cells) and comparatively less metastatic prostate cancer cells (LNCaP and DU145 cells). However, Kv2.1 expression was significantly decreased when the cells were treated with antioxidants, such as N-acetylcysteine or ascorbic acid, implying that the highly expressed Kv2.1 could detect reactive oxygen species (ROS) in malignant prostate cancer cells. In addition, the blockade of Kv2.1 with stromatoxin-1 or siRNA targeting Kv2.1 significantly inhibited the migration of malignant prostate cancer cells. Our results suggested that Kv2.1 plays an important role as a ROS sensor and that it is a promising therapeutic molecular target in metastasis of prostate cancer.