• Biomolecules & Therapeutics
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• v.23 no.5
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• pp.434-441
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• 2015

Histone deacetylase (HDAC) inhibitors are considered novel agents for cancer chemotherapy. We previously investigated MHY219, a new HDAC inhibitor, and its potent anticancer activity in human prostate cancer cells. In the present study, we evaluated MHY219 molecular mechanisms involved in the regulation of prostate cancer cell migration. Similar to suberanilohydroxamic acid (SAHA), MHY219 inhibited HDAC1 enzyme activity in a dose-dependent manner. MHY219 cytotoxicity was higher in LNCaP ($IC_{50}=0.67{\mu}M$) than in DU145 cells ($IC_{50}=1.10{\mu}M$) and PC3 cells ($IC_{50}=5.60{\mu}M$) after 48 h of treatment. MHY219 significantly inhibited the HDAC1 protein levels in LNCaP and DU145 cells at high concentrations. However, inhibitory effects of MHY219 on HDAC proteins levels varied based on the cell type. MHY219 significantly inhibited LNCaP and DU145 cells migration by down-regulation of matrix metalloprotease-1 (MMP-1) and MMP-2 and induction of tissue inhibitor of metalloproteinases-1 (TIMP-1). These results suggest that MHY219 may potentially be used as an anticancer agent to block cancer cell migration through the repression of MMP-1 and MMP-2, which is related to the reduction of HDAC1.

• Biomolecules & Therapeutics
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• v.28 no.2
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• pp.184-194
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• 2020

Histone deacetylase (HDAC) inhibitors represent a novel class of anticancer agents, which can be used to inhibit cell proliferation and induce apoptosis in several types of cancer cells. In this study, we investigated the anticancer activity of MHY4381, a newly synthesized HDAC inhibitor, against human prostate cancer cell lines and compared its efficacy with that of suberoylanilide hydroxamic acid (SAHA), a well-known HDAC inhibitor. We assessed cell viability, apoptosis, cell cycle regulation, and other biological effects in the prostate cancer cells. We also evaluated a possible mechanism of MHY4381 on the apoptotic cell death pathway. The IC₅₀ value of MHY4381 was lower in DU145 cells (IC₅₀=0.31 µM) than in LNCaP (IC₅₀=0.85 µM) and PC-3 cells (IC₅₀=5.23 µM). In addition, the IC₅₀ values of MHY4381 measured in this assay were significantly lower than those of SAHA against prostate cancer cell lines. MHY4381 increased the levels of acetylated histones H3 and H4 and reduced the expression of HDAC proteins in the prostate cancer cell lines. MHY4381 increased G2/M phase arrest in DU145 cells, and G1 arrest in LNCaP cells. It also activated reactive oxygen species (ROS) generation, which induced apoptosis in the DU145 and LNCaP cells by increasing the ratio of Bax/Bcl-2 and releasing cytochrome c into the cytoplasm. Our results indicated that MHY4381 preferentially results in antitumor effects in DU145 and LNCaP cells via mitochondria-mediated apoptosis and ROS-facilitated cell death pathway, and therefore can be used as a promising prostate cancer therapeutic.

• Food Science and Preservation
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• v.30 no.2
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• pp.358-368
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• 2023

Euonymus alatus (Thunb.) Sieb., also known as the arrow tree in Korea, is a plant in East Asia used in traditional medicine and food. In particular, the wings of E. alatus are rich in phenolic compounds. This study evaluated the antioxidant, α-glucosidase inhibition, and anti-cancer activities of E. alatus wing extracts. The radical and hydrogen peroxide scavenging acitvities and reducing the power of 1,000 ㎍/mL E. alatus wing extracts, were similar to those of the positive control (0.1% BHT, 0.1% α-tocopherol). In addition, ethanol and methanol extract at 250 ㎍/mL showed 95.70 and 94.99% of α-glucosidase inhibition activity, respectively. The ethanol extract of E. alatus wings had the highest total polyphenol and flavonoid contents (867.8 mg% and 521.7 mg%, respectively). The E. alatus wing extracts significantly decreased the cell viability of LNCaP human prostate cancer cells (p<0.001), MDA-MB-231 human breast cancer cells (p<0.001), and HT-29 human colon cancer cells (p<0.001) in a dose-dependent manner. However, there was no significant effect on B16 mouse melanoma cells. Notably, the ethanol extracts showed higher cancer cell growth inhibitory activity in LNCaP and HT-29 cells than the other extracts. These results suggest that E. alatus wing extracts could have significant clinical applications, and our results can be used as basic data for future functional food material development.

• KOREAN JOURNAL OF CROP SCIENCE
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• v.53 no.1
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• pp.75-84
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• 2008

Colored potatoes are an excellent source of dietary polyphenols including anthocyanins. Generally, anthocyanins from fruits and vegetables exhibit anti-carcinogenesis and anti-cancer properties in vitro test. This experiment was conducted to know the effects of colored potato extracts contained anthocyanins on antimutagenic activity and anticancer activity to six human cancer cell lines containing LNCaP (androgen-dependent) prostate cancer cells. Extracts of three colored potatoes ('Hongyoung', 'Jayoung' and 'Jasim') and the white potato ('Superior') cultivars were used in this study. The extracts of three colored potatoes inhibited the mutagenicities induced by direct mutagen such as 4-nitro-quinoline-1-oxide (4-NQO) and another indirect mutagens of bezo(a)pyrene (BaP). Also, the extracts of 'Hoyoung' and 'Jayoung' showed higher antimutagenic activity than 'Jasim' and 'Superior' against to direct or indirect mutagen on both strains of TA98 and TA100. The activity of growth-inhibitory of extract of four potato cultivars were screened by SRB (sulphorhodamine B) method on diverse human cancer cells representing different types of cancers. Among the extract of four potato cultivars, the extract of 'Jasim' showed moderate inhibition on proliferation of LNCaP, ACHN and MOLT-4F cells and did not inhibit the proliferation of other cancer cells. On the other hand, extract of 'Superior' did not inhibit the proliferation of any tested cancer cell lines. However, the extracts of 'Hongyoung and Jayoung' inhibited the proliferation of cancer cells with $GI_{50}$ values ranging from 2.5 to $30\;{\mu}g/mL$. On the basis of the $GI_{50}$ values, it is clear that LNCaP cells were more sensitive to extracts of colored potato cultivars than other cancer cells. The extract of 'Jayoung' at $30\;{\mu}g/mL$ were more active and inhibited cell proliferation, and induced apoptosis in LNCaP cells. This result revealed that the extracts of colored potatoes are expected to be good candidate for development into source of antimutagenic and anticancer agent.

• Journal of Mushroom
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• v.15 no.4
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• pp.244-248
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• 2017

In this study, the inhibitory effect of Paecilomyces tenuipes extract on PSA and angiogenesis-related factor expression levels were investigated in human prostate cancer cells, LNCaP. P. tenuipes extract significantly inhibited PSA expression in a dose-dependent manner. We also investigated the inhibitory effect of P. tenuipes extract on the expression of angiogenesis-related genes including VEGF, MMP-2, MMP-9, TIMP-1, and TIMP-2. P. tenuipes extract significantly down-regulated the expression of MMP-2 and MMP-9 in a dose-dependent manner. On the contrary, P. tenuipes increased the expression of TIMP-1 and TIMP-2. Our findings indicate that P. tenuipes exhibits an inhibitory effect on angiogenesis in human prostate cancer cells.

• Journal of Life Science
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• v.31 no.10
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• pp.885-897
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• 2021

Schisandrae Fructus (SF) and Corni Fructus (CF) have been used for a long time for the prevention and treatment of various diseases. Although reports have highlighted the possibility of inhibiting the onset and progression of benign prostatic hyperplasia (BPH), studies on related mechanisms are still lacking. In this study, we investigated the potential of SF and CF in improving BPH by using a dihydrotestosterone (DHT)-induced in vitro BPH model using LNCaP prostate carcinoma cells. According to our results, water and ethanol extracts of SF and CF significantly inhibited the proliferation of LNCaP cells by DHT treatment and markedly downregulated the expression of DHT-induced BPH biomarkers and growth factors. They also regulated the expression of apoptosis regulatory factors and significantly reduced DHT-mediated oxidative stress. In addition, the protective effect on major factors involved in the pathogenesis of BPH was more effective in the ethanol extract treatment group than in the water extract group. Furthermore, the improvement effect on BPH was higher in the 1:1 combined treatment group than in the ethanol extract alone treatment group of SF and CF, and 60% ethanol extracts showed a better effect than 40% ethanol extracts. Therefore, our findings demonstrate that SF and CF can protect against BPH by preventing the hyperproliferation of prostate cells through the inhibition of the androgen signaling pathway, which was correlated with their antioxidant activities. Therefore, SF and CF extracts may be useful in the clinical treatment of BPH, and the combination of these two extracts can be synergistic.

• Journal of Ginseng Research
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• v.20 no.3
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• pp.219-225
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• 1996

This study was performed to investigate the inhibition mechanism of cancer cell proof iferation caused by the petroleum-ether extract of ginseng against human rectum (HRT-18), colon (HT-29), llepatoma (Hep G2) and prostate (LNCaP) cancer cells and monkey kidney cells (Vero 76). Cells were treated with the petroleum-ether extract of ginseng (50 to 200 $\mu\textrm{g}$/ml) in G1 or S phase of the cell cycle, and proliferation and protein kinase C activity were measured. The petroleum-eth or extract of ginseng inhibited proliferation of HRT-18, HT-29, Hep G2 and LNCaP when treated in Gl phase, but not in S phase. This result shows that the ginseng extract arrests the cell cycle in G1 phase, resulting in the inhibition of cell proliferation. At the same concentrations, treatment of the ginseng extract in G1 phase decreased protein kinase C activity, while the treatment in S phase had no effect. This reault suggests that protein kinase C might be involved in the inhibition of the cell cycle and proliferation of cancer cells caused by the petroleum-ether extract of ginseng.

• 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.

• Natural Product Sciences
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• v.5 no.2
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• pp.97-103
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• 1999

The enzyme steroid $5{\alpha}-reductase$ is responsible for the conversion of testosterone into the most potent androgen dihydrotestosterone (DHT). In man, this steroid acts on a variety of androgen-responsive target tissues to mediate such diverse endocrine processes as male sexual differentiation in the fetus and prostatic growth in men. Androgen levels in the prostate may influence carcinogenesis in this organ. The use of a $5{\alpha}-reductase$ inhibitor, finasteride, in the chemoprevention of prostate cancer is being evaluated in a clinical trial and have been used successfully for treatment of benign prostatic hyperplasia. Therefore, for the discovery of $5{\alpha}-reductase$ type 2 inhibitors, we have evaluated the inhibitory effects of solvent fractionated extracts of natural products on $5{\alpha}-reductase$ type 2 activity. We have tested approximately 80 kinds of natural products after partition into n-hexane, ethyl acetate and aqueous layers from 100% methanol extracts of plants. The ethyl acetate fractions of Perilla sikokiana $(seed,\;IC_{50}\;:\;6.2\;ug/ml)$, Sophora flavescens $(root,\;IC_{50}\;:\;8.9\;ug/ml)$, and Angelica tenuissima $(root,\;IC_{50}\;:\;11.7\;ug/ml)$ revealed inhibitory effects on $5{\alpha}-reductase$ 2 activity in LNCaP cells. The effective ethyl acetate fractions of Perilla sikokiana, Sophora flavescens, Hydnocarpus anthelmintica, and Angelica tenuissima were subfractionated by column chromatography and tested. The subfractions $F4\;(IC_{50}\;:\;1.1\;ug/ml),\;F5\;(IC_{50}\;:\;2.0\;ug/ml),\;and\;F6\;(IC_{50}\;:\;5.8\;ug/ml)$ of the ethyl acetate fraction of Perilla sikokiana and the subfraction $F8\;(IC_{50}\;:\;5.3\;ug/ml)$ of the ethyl acetate fraction of Sophora flavescens displayed greater inhibition of $5{\alpha}-reductase$ type 2 than did finasteride in LNCaP cells. These active fractions are under the process of further sequential fractionation to find the effective pure compounds against $5{\alpha}-reductase$ 2 activity.

• 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.