• Title/Summary/Keyword: prostate cancer cells

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Induction of Apoptotic Cell Death and Depression of Bcl-2 Protein Levels by Trans-10,cis-12 Conjugated Linoleic Acid in Human Prostate Cancer (인간 전립선 암세포인 TSU-Pr1에서 trans-10,cis-12 Conjugated Linoleic Acid에 의한 Apoptosis 유발과 Bcl-2 단백질의 발현억제)

  • 오윤신;김은지;이상곤;정차권;강일준;신현경;윤정한
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.31 no.6
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    • pp.1126-1133
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    • 2002
  • Conjugated linoleic acid (CLA) is a collective term for a class of positional and geometric conjugated dienoic isomers of linoleic acid (LA) and has anti-cancer activity in experimental animals. We have previously observed that an isomeric mixture of CLA and trans-10,cis-12 (t10c12) inhibited cell growth in a dose-dependent manner whereas LA and cis-9,trans-11 (c9t11) had no effect. The present study examined whether the CLA mixture and t10c12 induce apoptotic cell death. TSU-Prl cells were incubated for three days in serum-free medium in the absence or presence of individual fatty acids, and the DNA fragmentation assay was performed. Cells treated with the CLA mixture or t10c12 produced a distinct oligonucleosomal ladder with different sizes of DNA fragments, a typical characteristic of cells undergoing apoptosis. By contrast, LA and c9t11 had no effect. Western immunoblot analysis of total lysates revealed that t10c12 reduced anti-apoptotic, 26 kDa, Bcl-2 protein levels by 49$\pm$8% compared with controls, whereas this CLA isomer did not alter pro-apoptotic,21 kDa, Bax protein levels. These results suggest that growth inhibitory effect of the t10c12 CLA isomer may, at least in part, be attributed to Increased apoptotic death in TSU-Prl cells.

Structural Basis for Recognition of L-lysine, L-ornithine, and L-2,4-diamino Butyric Acid by Lysine Cyclodeaminase

  • Min, Kyungjin;Yoon, Hye-Jin;Matsuura, Atsushi;Kim, Yong Hwan;Lee, Hyung Ho
    • Molecules and Cells
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    • v.41 no.4
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    • pp.331-341
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    • 2018
  • L-pipecolic acid is a non-protein amino acid commonly found in plants, animals, and microorganisms. It is a well-known precursor to numerous microbial secondary metabolites and pharmaceuticals, including anticancer agents, immunosuppressants, and several antibiotics. Lysine cyclodeaminase (LCD) catalyzes ${\beta}$-deamination of L-lysine into L-pipecolic acid using ${\beta}$-nicotinamide adenine dinucleotide as a cofactor. Expression of a human homolog of LCD, ${\mu}$-crystallin, is elevated in prostate cancer patients. To understand the structural features and catalytic mechanisms of LCD, we determined the crystal structures of Streptomyces pristinaespiralis LCD (SpLCD) in (i) a binary complex with $NAD^+$, (ii) a ternary complex with $NAD^+$ and L-pipecolic acid, (iii) a ternary complex with $NAD^+$ and L-proline, and (iv) a ternary complex with $NAD^+$ and L-2,4-diamino butyric acid. The overall structure of SpLCD was similar to that of ornithine cyclodeaminase from Pseudomonas putida. In addition, SpLCD recognized L-lysine, L-ornithine, and L-2,4-diamino butyric acid despite differences in the active site, including differences in hydrogen bonding by Asp236, which corresponds with Asp228 from Pseudomonas putida ornithine cyclodeaminase. The substrate binding pocket of SpLCD allowed substrates smaller than lysine to bind, thus enabling binding to ornithine and L-2,4-diamino butyric acid. Our structural and biochemical data facilitate a detailed understanding of substrate and product recognition, thus providing evidence for a reaction mechanism for SpLCD. The proposed mechanism is unusual in that $NAD^+$ is initially converted into NADH and then reverted back into $NAD^+$ at a late stage of the reaction.

Evaluation of Antioxidant and Anticancer Activity of Steam Extract from The Bamboo Species

  • Kim, Ji-Su;Lee, Hyung Chul;Jo, Jong-Soo;Jung, Ji Young;Ha, Yeong Lea;Yang, Jae-Kyung
    • Journal of the Korean Wood Science and Technology
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    • v.42 no.5
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    • pp.543-554
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    • 2014
  • Natural plant extract has been the subject of intense research aiming in elucidating the underlying mechanisms of their chemopreventive effects upon various forms of human cancers. The objective of our study was to evaluate the natural antioxidants and anticancer agent potential of Phyllostachys. The chemical composition of steam extract from Phyllostachys was carried out using GC-MS. The steam extract of Phyllostachys was dominated by monoterpenes (62.96% - 71.36%) and sesquiterpenes (23.58% - 33.13%) as the main compounds. The antioxidant activities of the steam extract was determined using a DPPH scavenging and hydrogen peroxide scavenging activity test systems. Furthermore, the amounts of total phenolics in steam extract were determined spectrometrically The steam extract of P. pubescens and P. bambusoides were presented the high activity (69.4% and 64.0%, respectively.). The steam extract from Pyllostachys species showed a hydrogen peroxide scavenging activity of approximately 50.4% - 54.6% when compared to that of the standard gallic acid. The anticancer activities of steam extract were determined using a MTT assay. Assessment of the cytotoxic effect of the steam extract on PC-3 cells showed that the P. bambusoides (20.85%) and P. pubescens (20.41%) were superior in induced cytotoxicity compared with the steam extract of P. nigra var. henonis (1.15%). Findings from this study indicated that steam extract of P. bambusoides and P. pubescens possessed potential as medicinal drug especially in prostate cancer treatment.

Mechanism of Inhibition of Human Cytochrome P450 1A1 and 1B1 by Piceatannol

  • Chae, Ah-Reum;Shim, Jae-Ho;Chun, Young-Jin
    • Biomolecules & Therapeutics
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    • v.16 no.4
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    • pp.336-342
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    • 2008
  • The resveratrol analogue piceatannol (3,5,3',4'-tetrahydroxy-trans-stilbene) is a polyphenol present in grapes and wine and reported to have anti-carcinogenic activities. To investigate the mechanism of anticarcinogenic activities of piceatannol, the effects on CYP 1 enzymes were determined in Escherichia coli membranes coexpressing recombinant human CYP1A1, CYP1A2 or CYP1B1 with human NADPH-P450 reductase. Piceatannol showed a strong inhibition of CYP1A1 and CYP1B1 in a concentration-dependent manner, and $IC_{50}$ of human CYP1A1 and CYP1B1 was 5.8 ${\mu}M$ and 16.6 ${\mu}M$, respectively. However, piceatannol did not inhibit CYP1A2 activity in the concentration of up to 100 ${\mu}M$. Piceatannol exhibited 3-fold selectivity for CYP1B1 over CYP1A1. The mode of inhibition of piceatannol was non-competitive for CYP1A1 and CYP1B1. The result that piceatannol did not inhibit CYP1B1-mediated $\alpha$-naphthoflavone ($\alpha$-NF) metabolism suggests piceatannol may act as a non-competitive inhibitor as well. In human prostate carcinoma PC-3 cells, piceatannol induces apoptosis and prevents Aktmediated signal pathway. Taken together, abilities of piceatannol to induce apoptotic cell death as well as CYP1 enzyme inhibition make this compound a useful tool for cancer chemoprevention.

Radiopharmaceuticals for the Therapy of Metastatic Bone Pain (뼈전이의 방사성동위원소 통증치료)

  • Ahn, Byeong-Cheol
    • Nuclear Medicine and Molecular Imaging
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    • v.40 no.2
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    • pp.82-89
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    • 2006
  • Bone metastasis is a common sequelae of solid malignant tumors such as prostate, breast, lung, and renal cancers, which can lead to various complications, including fractures, hypercalcemia, and bone pain, as well as reduced performance status and quality of life it occurs as a result of a complex pathophysiologic process between host and tumor cells leading to cellular invasion, migration adhesion, and stimulation of osteoclastic and osteoblastic activity. Several sequelae occur as a result of osseous metastases and resulting bone pain can lead to significant debilitation. A multidisciplinary approach is usually required not only to address the etiology of the pain and its complicating factors but also to treat the patient appropriately. Pharmaceutical therapy of bone pain, includes non-steroidal analgesics, opiates, steroids, hormones, bisphosphonates, and chemotherapy. While external beam radiation therapy remains the mainstay of pain palliation of a solitary lesions, bone seeking radiopharmaceuticals have entered the therapeutic armamentarium for the treatment of multiple painful osseous lesions. $^{32}P,\;^{89}SrCl,\;^{153}Sm-EDTMP,\;^{188}Re/^{186}Re-HEDP,\;and\;^{177}Lu-EDTMP$ can be used to treat painful osseous metastases. These various radiopharmaceuticals have shown good efficacy in relieving bone pain secondary to bone metastasis. This systemic form of metabolic radiotherapy is simple to administer and complements other treatment options. This has been associated with improved mobility in many patients, reduced dependence on narcotic and non-narcotic analgesics, improved performance status and quality of life, and, in some studios, improved survival. All of these agents, although comprising different physical and chemical characteristics, offer certain advantages in that they are simple to administer, are well tolerated by the patient if used appropriately, and can be used alone or in combination with the other forms of treatment. This article illustrates the salient features of these radiopharmaceuticals, including the usual therapuetic dose, method of administration, and indications for use and also describe about the pre-management checklists, and jndication/contraindication and follow-up protocol.

Antioxidant and antiproliferating effects of Setaria italica, Panicum miliaceum and Sorghum bicolor extracts on prostate cancer cell lines (조, 기장, 수수 추출물의 항산화 효과 및 전립선 암세포주 증식 억제 효능)

  • Kim, Jeong-Ho;Cho, Hyun-Dong;Hong, Seong-Min;Lee, Ju-Hye;Lee, Yong-Seok;Kim, Du-Hyun;Seo, Kwon-Il
    • Food Science and Preservation
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    • v.23 no.7
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    • pp.1033-1041
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    • 2016
  • In this study, we evaluated antioxidant and antiproliferating effects of Setaria italica extract (SIE), Panicum miliaceum extract (PME) and Sorghum bicolor extract (SBE). Antioxidant effects of these extracts were determined by assessing DPPH radical scavenging activity, $ABTS^+$ radical scavenging activity, reducing power and superoxide dismutase (SOD)-like activity. From high concentrations ($1,000{\mu}g/mL$) of each extract at DPPH radical scavenging activities of SIE, PME and SBE were 10.5%, 5.5% and 86.8% respectively, $ABTS^+$ radical activities were 4.92%, 5.9% and 62.3% respectively, reducing powers (OD 700) were 0.15, 0.18 and 1.7 respectively, and SOD-like activities were 17.0%, 15.9% and 38.6% respectively. In addition, SBE significantly decreased the cell viability of androgen-sensitive lymph node metastasis type of prostate cancer (LNCaP) cells in a dose-dependent manner. Morphological study of SBE-treated LNCaP cells revealed distorted and shrunken cell masses. SBE-induced cell death was confirmed by observation of nuclear condensation and increased formation of apoptotic bodies. The antiproliferative effect of SBE seems to be associated with the antioxidant activity of its polyphenol content. The results of this study indicate that SBE can exert antioxidant and antiproliferative effects and may be as a useful food material.

Biological Activities in the Leaf Extract of Lythrum salicaria L. (털부처꽃 잎 추출물의 생리활성탐색)

  • Kim, Hee-Yeon;Lim, Sang-Hyun;Park, Min-Hee;Park, Yu-Hwa;Ham, Hun-Ju;Lee, Ki-Yun;Park, Dong-Sik;Kim, Kyung-Hee;Kim, Song-Mun
    • Korean Journal of Medicinal Crop Science
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    • v.18 no.6
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    • pp.409-415
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    • 2010
  • In this study, the bioactivities of ethanol (EELS) and water extract (WELS) from the leaf of Lythrum salicaria L. were investigated. In the anti-cancer activity, the growths of both human prostate cancer (DU145) and human colonic carcinoma cell (HT29) were inhibited up 60% by adding 10 mg/$m{\ell}$ of EELS. Anti-inflammatory activity of EELS and WELS have been evaluated on lipopolysaccharide (LPS) induced release of nitric oxide (NO) by the macrophage RAW 264.7 cells. EELS and WELS inhibited inflammatory by 57.3 and 46.9% in 10 mg/$m{\ell}$, respectively. In the anti-oxidative activity, $IC_{50}$ of DPPH radical scavenging activity was respectively 60.71 and $92.90\;{\mu}g/m{\ell}$ by EELS and WELS. In the anti-diabetic activity, $IC_{50}$ of ${\alpha}$-amylase inhibitory activity of EELS and WELS were respectively 5,250 and $5,020\;{\mu}g/m{\ell}$. $IC_{50}$ of ${\alpha}$-glucosidase inhibitory activity was 7.96 and $68.41\;{\mu}g/m{\ell}$ by EELS and WELS. In the anti-obesity, $IC_{50}$ of lipase inhibitory activity was 880 and $9,840\;{\mu}g/m{\ell}$ by EELS and WELS. Finally, EELS and WELS exhibited anti-oxidative, anti-inflammatory, anti-diabetic activity and anti-obesity. It suggests that Lythrum salicaria L. could be potentially used as a resource of bioactive materials for health functional foods.

Anti-oxidant and Anti-proliferative Effects of Water Extract Mixture of Cordyceps Militaris and Allium Tuberosum (동충하초 및 부추 혼합 물추출물의 항산화 및 암세포 증식억제 효과)

  • Hong, Seong-Min;Cho, Hyun-Dong;Kim, Jeong-Ho;Lee, Jae-Yoon;Park, Jeong-Mee;Seo, Kwon-Il
    • Journal of Life Science
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    • v.26 no.7
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    • pp.805-811
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    • 2016
  • The present study was performed to evaluate the anti-oxidant and anti-proliferating activity of the water extract mixture of Cordyceps militaris (CM) and Allium tuberosum (AT). The water extract mixture rate of CM and AT was optimized by means of a sensory evaluation test. The optimized mixture rate were decided at 70% of CM, 30% of AT, and 10% of apple concentrate as an additive. The values of total acidity, pH, sugar contents, and turbidity of the water extract mixture were 0.1%, 4.28, 9.10 °Brix, and 1.48 respectively. The water extract mixture had effective DPPH radical scavenging activity, reducing power effect, and ABTS radical activity. DPPH radical activities of the water extract and the water extract mixture were 43.2% and 51.7% respectively; their reducing power (OD700) was 1.14 and 1.43 respectively; and ABTS.+ radical activities were 47.1% and 62.2% respectively. Also, the water extract mixture showed a higher anti-proliferating effect than the AT extract on human prostate cancer cells. These results provided experimental evidence that the water extract mixture of CM and AT is a better source of anti-oxidant and anti-cancer ingredients than a single extract of CM. In conclusion, the water extract mixture of CM and AT will be beneficial in development of a functional drink.

Purification of Recombinant CTP-Conjugated Human prostatic acid phosphatase for activation of Dendritic Cell (수지상세포 활성화를 위한 세포투과 펩타이드가 결합된 재조합 전립성 산성 인산분해효소의 정제)

  • Yi, Ki-Wan;Ryu, Kang
    • KSBB Journal
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    • v.24 no.1
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    • pp.80-88
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    • 2009
  • Human prostatic acid phosphatase (PAP), with comprehensive homology to glandular kallikrein, are representative serum biomarkers of prostate cancer. Dendritic cell (DC), which is the potent antigen-presenting cells(APC) in the immune system, can induce strong T cell responses against viruses, microbial pathogens, and tumors. Therefore, the immunization using DC loaded with tumor-associated antigens is a powerful method for inducing anti-tumor immunity. The CTP (Cytoplasmic Transduction Peptide) technology developed by Creagene which can transport attached bio-polymers like nucleic acids or proteins into the cell with high permeation efficiency. As the active forms of PAP can mediate apoptotic processing, we used multimer forms of PAP as an inactive form for antigen pulsing of DCs. In this study, multimeric forms of CTP-rhPAP was obtained according to the advanced purification process and subsequently confirmed by gel filtration chromatography, western blot and Dynamic Light Scattering. Therefore, CTP-conjugated PA multimers transduced into the cytoplasm were efficiently presented on the cell surface without any harm effect on cells via MHC class I molecules and result in induction of a large number of effector cell.

The Ethanol Extract of Red Ginseng Enhances Anti-Tumor Effects Using Co60 Gamma Irradiation (홍삼의 에탄올 추출물의 감마선 조사를 통한 항암효과 증대)

  • Hur, Jung-Mu;Kim, Dong-Ho
    • Journal of Applied Biological Chemistry
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    • v.54 no.1
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    • pp.15-20
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    • 2011
  • Red ginseng is one of the most popular traditional medicines in Korea. In this study, we developed a new technique in which ethanol extract of $\underline{r}$ed $\underline{g}$inseng (HRG) was exposed to the $Co^{60}$ gamma radiation ranging from 1~5 kGy. The irradiated HRG (IHRG) were analyzed by high performance liquid chromatography (HPLC) to determine any compositional changes of ginsenosides due to irradiation. No appreciable difference was observed in the HPLC pattern of ginsenosides of HRG. Using MTT assay, the cytotoxicity effect was significantly increased by IHRG compared to HRG. The $LD_{50}$ concentration was $30{\mu}g/mL$ for IHRG-1 (1 kGy), and $15{\mu}g/mL$ for IHRG-5 (5 kGy). The evidences of apoptosis, such as nuclei cleavage and Annexin V staining, were observed in the human prostate cancer PC-3 cells treated with the IHRG. Additionally, the level of reactive oxygen species (ROS) was apparently elevated by IHRG. We also studied the inhibitory effect of IHRG on the growth rate of tumor xenografts in BALB/c male mice. The tumor growth rates were inhibited by 56.9 and 76.1% in mice treated with 10 mg/kg of IHRG-1 and IHRG-5, respectively, compared with control group (21.1%). These results suggest that some biologically active and soluble components in HRG can be more effectively enhancement of anti-tumor effects using irradiation.