Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
35 巻 , 1 号
選択された号の論文の20件中1~20を表示しています
Regular Articles
  • Hitoshi Kotani, Hiroki Tanabe, Hajime Mizukami, Sakae Amagaya, Makoto ...
    原稿種別: Regular Article
    2012 年 35 巻 1 号 p. 1-9
    発行日: 2012/01/01
    公開日: 2012/01/05
    ジャーナル フリー
    We investigated the properties of honokiol, a natural rexinoid, as a regulator of retinoid X receptor (RXR) heterodimers with various partner nuclear receptors (NRs), in comparison with those of the synthetic rexinoid bexarotene. Honokiol alone was hardly capable of activating peroxisome proliferator-activated receptor (PPAR) γ/RXR, RXR/liver X receptor (LXR), and RXR/vitamin D receptor (VDR) heterodimers, whereas it effectively potentiated their activation by agonists for the partner NRs of the RXR heterodimers. These findings were further supported by increased mRNA and protein levels for the respective NR target genes. Bexarotene alone activated PPARγ/RXR and RXR/LXR heterodimers, but not RXR/VDR heterodimers, and facilitated the activation of all three RXR heterodimers by the respective PPARγ, LXR, and VDR agonists. When the potencies of honokiol and bexarotene were compared, honokiol was able to serve as a subsidiary agonist in the activation of RXR heterodimers in a similar manner to bexarotene. However, it seemed to potentiate the activation of PPARγ/RXR heterodimers by the PPARγ agonist rosiglitazone more efficiently than bexarotene, and was a less potent RXR agonist than bexarotene. In conclusion, we have demonstrated that honokiol is a rexinoid that possesses distinct properties from bexarotene, and mainly has subsidiary roles in the activation of RXR heterodimers by potentiating the activation of RXR heterodimers by agonists for the partner NRs.
  • Mai Ishibashi, Mariko Arai, Sachiko Tanaka, Kenji Onda, Toshihiko Hira ...
    原稿種別: Regular Article
    2012 年 35 巻 1 号 p. 10-17
    発行日: 2012/01/01
    公開日: 2012/01/05
    ジャーナル フリー
    The effects of six lipophilic vitamins: tretinoin (ATRA), vitamin D3 (VD3), VE, VK1, VK3, and VK5 on cell proliferation and apoptosis in human A375 melanoma cells were investigated. VD3, VK3, and VK5 were found to inhibit cell proliferation significantly at concentration ranges of 10—100 μmol/L (p<0.01), while the other vitamins did not show inhibitory effects at 100 μmol/L. VK3 and VK5 showed the strongest effects with IC50 values of less than 10 μmol/L. Dacarbazine slightly inhibited the proliferation of A375 cells at a concentration range of 25—100 μmol/L, but the effects were not statistically significant. VK3 and VK5 increased annexin-V positive apoptotic cells, as well as activating caspase-3, in A375 cells. Our findings showed that VD3, VK3, and VK5 inhibited the growth of dacarbazine resistant human melanoma cells, while ATRA, VE, and VK1 had little effect on the cell growth. The effects of VK3 and VK5 were observed at concentrations lower than 10 μmol/L, which are suggested to have resulted from apoptosis-induction in the melanoma cells.
  • Mayumi Kaneko, Daisuke Matsuda, Masaki Ohtawa, Takashi Fukuda, Tohru N ...
    原稿種別: Regular Article
    2012 年 35 巻 1 号 p. 18-28
    発行日: 2012/01/01
    公開日: 2012/01/05
    ジャーナル フリー
    Most cancer cells have mutations in genes at the G1 checkpoint and repair DNA only in the G2 phase; therefore, the G2 checkpoint is a potential target to develop novel therapy. In the course of screening, a known compound, pycnidione, was isolated from the fungal culture broth of Gloeotinia sp. FKI-3416. Pycnidione irreversibly abrogated bleomycin-induced G2 arrest in Jurkat cells and synergically potentiated the cytotoxicity of bleomycin. To elucidate the mechanism of action, the effect of pycnidione on the signal transduction of the G2 checkpoint was analyzed, showing that the increased phospho-cyclin dependent kinase-1 (CDK1) level caused by bleomycin was abrogated in the presence of pycnidione, indicating that cells did not arrest at the G2 phase. Moreover, under these conditions, Chk1 and Chk2 levels were markedly down-regulated. Thus, we concluded that pycnidione abrogated bleomycin-induced G2 arrest by decreasing Chk1 and Chk2.
  • Sunanta Tangnitipong, Thitiporn Thaptimthong, Sirada Srihirun, Supeenu ...
    原稿種別: Regular Article
    2012 年 35 巻 1 号 p. 29-33
    発行日: 2012/01/01
    公開日: 2012/01/05
    ジャーナル フリー
    Artemisinin exerts the antimalarial activity through activation by heme. The hemolysis in malaria results in the elevated levels of plasma heme which may affect the activity of artemisinin. We hypothesized that the extracellular heme would potentiate the antimalarial activity of artemisinin. Hemin (ferric heme) at the pathologic concentrations enhanced the activity of artemisinin against Plasmodium falciparum in vitro and increased the levels of the lipid peroxidation products in the presence of artemisinin. The antimalarial activity of artemisinin and potentiation by hemin was decreased by vitamin E. Hemin had no effect on the activity of quinoline drugs (chloroquine, quinine and mefloquine). Furthermore, the oxidative effect of hemin in the presence of artemisinin or quinoline drugs was studied using low-density lipoprotein (LDL) oxidation as a model. Artemisinin enhanced the effects of hemin on lipid peroxidation and a decrease of tryptophan fluorescence in LDL whereas the quinoline drugs inhibited the oxidation by hemin. In conclusion, the extracellular hemin enhances the antimalarial activity of artemisinin as a result of the increasing oxidative effect of hemin.
  • Chan Hum Park, Takashi Tanaka, Eun Ju Cho, Jong Cheol Park, Naotoshi S ...
    原稿種別: Regular Article
    2012 年 35 巻 1 号 p. 34-41
    発行日: 2012/01/01
    公開日: 2012/01/05
    ジャーナル フリー
    The protective effect of 7-O-galloyl-D-sedoheptulose (GS), isolated from Corni Fructus as an active component, against acute renal failure (ARF) induced by glycerol was investigated. The administration of GS led to a decline in the levels of blood urea nitrogen and creatinine; on the other hand, it did not have a significant effect on creatinine clearance. Furthermore, GS also significantly decreased the urine volume and fractional excretion of sodium, but it increased the urine osmolarity, suggesting the protective role of GS against renal dysfunction. Oxidative stress under ARF was attenuated by GS through the inhibition of lipid peroxidation, scavenging of reactive oxygen species (ROS), and elevation of the antioxidative status. Renal oxidative stress is related to the overproduction of ROS by nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase; therefore, in the present study, the protein expression of p22phox and NAD(P)H oxidase-4 (Nox-4) was investigated. GS down-regulated the protein expression of p22phox; on the other hand, it did not significantly affect the expression of Nox-4. This indicates that GS inhibits the production of superoxide by regulating a component of NAD(P)H oxidase, p22phox. Furthermore, GS down-regulated the expressions of nuclear factor-κB (NF-κΒ) and inducible nitric oxide (NO) synthase (iNOS), suggesting that GS protects against NO-induced inflammatory pathological conditions under ARF through the regulation of NF-κB and iNOS expressions. The present study indicates that GS exerts a protective effect against ARF through the recovery of renal dysfunction and attenuation of renal oxidative stress by regulating related protein expression.
  • Chiyoko Uchiyama, Kazuhiro Ishida, Takuya Tsutsui, Atsushi Naito, Kei ...
    原稿種別: Regular Article
    2012 年 35 巻 1 号 p. 42-47
    発行日: 2012/01/01
    公開日: 2012/01/05
    ジャーナル フリー
    Neurotrophin (NT)-4 is known to be an inducer of catagen in the hair cycle, but little is known of its role in the pathogenesis of androgenetic alopecia (AGA). We previously studied the gene expression of dermal papilla cells from AGA patients and controls and found that NT-4 was up-regulated in the AGA patients. In the present study, the etiological relationship between NT-4 and androgen, which is one of the causes of AGA, and the effect of an NT-4 inhibitor on hair growth were investigated. We established a NT-4 luciferase reporter assay system using a roughly 2-kb region upstream of the NT-4 transcriptional start site and investigated an accelerating effect of androgen on NT-4 transcription. We also screened for a NT-4 inhibitor by using the NT-4 reporter assay and evaluated the effects of NT-4 inhibitors on hair growth by using dihydrotestosterone (DHT)-implanted mice. The results show that transcriptional activity of NT-4 was accelerated by androgen, and extract of Hura crepitans L. inhibited the DHT-induced NT-4 transcriptional activation and ameliorated the retardation of hair regrowth by DHT-implanted mice. We also isolated the active ingredient in H. crepitans and found its structure to be that of 6,7-epoxy-5-hydroxyresiniferonol-14-(2,4-tetradecadienoate), i.e., daphne factor F3. These findings demonstrated that NT-4 activity accelerated by androgen might contribute to the pathogenesis of AGA and indicated that NT-4 inhibitors such as H. crepitans and daphne factor F3 might have a salutary effect on AGA.
  • Kent Sakai, Nobuhiro Koyama, Takashi Fukuda, Yukiko Mori, Hiroyasu Ona ...
    原稿種別: Regular Article
    2012 年 35 巻 1 号 p. 48-53
    発行日: 2012/01/01
    公開日: 2012/01/05
    ジャーナル フリー
    Staphyloxanthin, a yellow pigment produced by methicillin-resistant Staphylococcus aureus (MRSA), is a virulent factor escaping from the host immune system. A new screening method for inhibitors of staphyloxanthin production by MRSA was established using paper disks. By this screening method, inhibitors of staphyloxanthin production were selected from the natural product library (ca. 300) and from actinomycete culture broths (ca. 1000). From the natural product library, four known inhibitors of lipid metabolism, cerulenin, dihydrobisvertinol, xanthohumol and zaragozic acid, were found to inhibit staphyloxanthin production; however, typical antibiotics used clinically, including vancomycin, had no effect on staphyloxanthin production. From actinomycete culture broths, two known anthraquinones, 6-deoxy-8-O-methylrabelomycin and tetrangomycin, were found to inhibit staphyloxanthin production by MRSA in the paper disk assay. These results suggested that this screening method is useful and effective to find compounds targeting staphyloxanthin production, leading to a new type of chemotherapeutics against MRSA infection.
  • Yusuke Ueno, Hiroko Matsuda, Hideki Mizutani, Takuya Iwamoto, Masahiro ...
    原稿種別: Regular Article
    2012 年 35 巻 1 号 p. 54-58
    発行日: 2012/01/01
    公開日: 2012/01/05
    ジャーナル フリー
    The aim of this study was to elucidate the characteristics of the transport of lactone and carboxylate forms of SN-38 (SN-38L and SN-38C, respectively), a metabolite of irinotecan hydrochloride (CPT-11), with the human intestinal epithelial cell line, Caco-2. We examined SN-38L and SN-38C uptake from the apical side into Caco-2, and the effects of various compounds on the uptake of SN-38L. SN-38L and SN-38C in the cells were determined by HPLC with a fluorescence detector. When either SN-38L (0.5 µM) or SN-38C (0.5 µM) was added extracellularly at 37°C, the accumulation of SN-38L into the cells was about 10-fold higher than that of SN-38C, suggesting a dominant role of the lactone form in the uptake of SN-38 into Caco-2. The accumulation of SN-38L in Caco-2 increased time-dependently up to 10 min at 37°C, whereas the accumulation markedly decreased at 4°C. The initial uptake rate of SN-38L approached saturation at high concentrations with Michaelis–Menten constant and ‘Hill coefficient,’ 2.84±1.00 μM and 2.13±1.14, respectively (mean±S.E.). The accumulation of SN-38L was markedly inhibited by baicalin, an active ingredient of a Chinese herbal medicine, Hange-Shashin-To, as well as CPT-11. The type of inhibition by baicalin was competitive. In contrast, concomitant sulfobromophthalein, taurocholate and estrone 3-sulfate significantly increased SN-38L uptake. These results suggest that apical uptake of SN-38 by Caco-2 is dominantly performed as a lactone form through a specific transporter, which is competitively inhibited by baicalin.
  • Takashi Kawaguchi, Satoru Iwase, Masayoshi Koinuma, Yuki Onodera, Hiro ...
    原稿種別: Regular Article
    2012 年 35 巻 1 号 p. 59-64
    発行日: 2012/01/01
    公開日: 2012/01/05
    ジャーナル フリー
    Although pharmacist counseling assumes an important role in the clinical setting, oncology pharmacy practitioners worldwide currently lack adequate guidance. This study aimed to identify the determinants and causal relationships that affect quality of life (QOL) in breast cancer patients before adjuvant systemic therapy for improving pharmacist counseling and guidance. This study analyzed 93 postoperative patients with breast cancer before pharmacist counseling for adjuvant systemic therapy. Patients were asked to complete questionnaires to assess QOL (the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 [EORTC QLQ-C30] and its breast cancer module [EORTC QLQ-BR23]) before pharmacist counseling. We analyzed factors affecting QOL by stepwise multiple linear regression analysis and evaluated causal association using path analysis. In the multiple linear regression model using variables selected by stepwise analysis, the factors affecting global health status (GHS)/QOL included fatigue, emotional functioning, systemic therapy side effects, future perspectives, and appetite loss. In the path analysis model, GHS/QOL were strongly influenced by fatigue directly; and emotional functioning, directly and indirectly via other factors. Our results indicated that fatigue and emotional functioning are strong factors affecting QOL. These factors may be able to predict poor QOL before initiating adjuvant systemic therapy. Thus, our findings suggest that these factors may be potentially useful for pharmacist counseling at the beginning of adjuvant systemic therapy.
  • Zheng Fu Tai, Guo Lin Zhang, Fei Wang
    原稿種別: Regular Article
    2012 年 35 巻 1 号 p. 65-71
    発行日: 2012/01/01
    公開日: 2012/01/05
    ジャーナル フリー
    Type I interferons (IFN-α/β) have been widely used in the treatment of many viral and malignant diseases by activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway, but the side effects of protein-based IFN therapy severely limit their clinical use. Discovering small molecules to activate the JAK/STAT pathway will greatly facilitate the development of new drugs which have similar pharmacological function to IFNs but with fewer side effects. To screen a natural products-based library, we established a cell-based screening assay using human hepatoma HepG2 cells stably transfected with a plasmid where the luciferase reporter activity is driven by interferon α-stimulated response element (ISRE), the motif specifically recognized by type I IFN-induced activation of JAK/STAT pathway. Among 1,431 natural product compounds screened, four compounds (emodin, quercetin, apigenin and luteolin) were identified as activators of the JAK/STAT pathway. Further studies demonstrated that these four compounds could increase the endogenous antiviral gene expression regulated by the IFN-activated JAK/STAT pathway. The identified small molecule activators are valuable for structural modification and warrant further investigation for use in new antiviral drugs as IFN mimics or adjuvants.
  • Shuichi Sato, Toshiki Hatanaka, Hironori Yuyama, Masashi Ukai, Yukiko ...
    原稿種別: Regular Article
    2012 年 35 巻 1 号 p. 72-77
    発行日: 2012/01/01
    公開日: 2012/01/05
    ジャーナル フリー
    We determined the binding affinity of tamsulosin, a selective α1-adrenoceptor antagonist, for human α1-adrenoceptor subtypes in comparison with those of other α1-adrenoceptor antagonists including silodosin, prazosin, 5-methylurapidil, terazosin, alfuzosin, nafopidil, urapidil and BMY7378. The association and dissociation kinetics of [3H]tamsulosin for recombinant human α1-adrenoceptor subtypes were compared with those of [3H]prazosin. Tamsulosin competitively inhibited [3H]prazosin binding to human α1A-, α1B- and α1D-adrenoceptors (pKi values were 10.38, 9.33, 9.85) indicating 11 and 3.4-fold higher affinities for human α1A-adrenoceptor than those for α1B- and α1D-adrenoceptors, respectively. The affinity of tamsulosin for the human α1A-adrenoceptor was, respectively, 5, 9.9, 38, 120, 280, 400, 1200 and 10000 fold higher than those of silodosin, prazosin, 5-methylurapidil, terazosin, alfuzosin, naftopidil, urapidil and BMY7378, respectively. [3H]Tamsulosin dissociated from the α1A-adrenoceptor slower than from the α1B- and α1D-adrenoceptors (α1B1D1A). Moreover, [3H]tamsulosin dissociated slower than [3H]prazosin from the α1A-adrenoceptor and faster from the α1B- and α1D-adrenoceptors. In conclusion, tamsulosin potently and selectively antagonized α1A/1D-adrenoceptor ligand binding, and slowly dissociated from the α1A-adrenoceptor subtype.
  • Megumi Masuda, Kimihisa Itoh, Kazuya Murata, Shunsuke Naruto, Akemi Uw ...
    原稿種別: Regular Article
    2012 年 35 巻 1 号 p. 78-83
    発行日: 2012/01/01
    公開日: 2012/01/05
    ジャーナル フリー
    The objective of this study was to examine the effects of Morinda citrifolia (noni) extract and its constituents on α-melanocyte stimulating hormone (α-MSH)-stimulated melanogenesis in cultured murine B16 melanoma cells (B16 cells). A 50% ethanolic extract of noni seeds (MCS-ext) showed significant inhibition of melanogenesis with no effect on cell proliferation. MCS-ext was more active than noni leaf and fruit flesh extracts. Activity guided fractionation of MCS-ext led to the isolation of two lignans, 3,3′-bisdemethylpinoresinol (1) and americanin A (2), as active constituents. To elucidate the mechanism of melanogenesis inhibition by the lignans, α-MSH-stimulated B16 cells were treated with 1 (5 μM) and 2 (200 μM). Time-dependent increases of intracellular melanin content and tyrosinase activity, during 24 to 72 h, were inhibited significantly by treatment with the lignans. The activity of 1 was greater than that of 2. Western blot analysis suggested that the lignans inhibited melanogenesis by down regulation of the levels of phosphorylation of p38 mitogen-activated protein kinase, resulting in suppression of tyrosinase expression.
  • Seisuke Mimori, Yasunobu Okuma, Masayuki Kaneko, Koichi Kawada, Toru H ...
    原稿種別: Regular Article
    2012 年 35 巻 1 号 p. 84-90
    発行日: 2012/01/01
    公開日: 2012/01/05
    ジャーナル フリー
    Endoplasmic reticulum (ER) stress responses play an important role in neurodegenerative diseases. Sodium 4-phenylbutyrate (4-PBA) is a terminal aromatic substituted fatty acid that has been used for the treatment of urea cycle disorders. 4-PBA possesses in vitro chemical chaperone activity and reduces the accumulation of Parkin-associated endothelin receptor-like receptor (Pael-R), which is involved in autosomal recessive juvenile parkinsonism (AR-JP). In this study, we show that terminal aromatic substituted fatty acids, including 3-phenylpropionate (3-PPA), 4-PBA, 5-phenylvaleric acid, and 6-phenylhexanoic acid, prevented the aggregation of lactalbumin and bovine serum albumin. Aggregation inhibition increased relative to the number of carbons in the fatty acids. Moreover, these compounds protected cells against ER stress-induced neuronal cell death. The cytoprotective effect correlated with the in vitro chemical chaperone activity. Similarly, cell viability decreased on treatment with tunicamycin, an ER stress inducer, and was dependent on the number of carbons in the fatty acids. Moreover, the expression of glucose-regulated proteins 94 and 78 (GRP94, 78) decreased according to the number of carbons in the fatty acids. Furthermore, we investigated the effects of these compounds on the accumulation of Pael-R in neuroblastoma cells. 3-PPA and 4-PBA significantly suppressed neuronal cell death caused by ER stress induced by the overexpression of Pael-R. Overexpressed Pael-R accumulated in the ER of cells. With 3-PPA and 4-PBA treatment, the localization of the overexpressed Pael-R shifted away from the ER to the cytoplasmic membrane. These results suggest that terminal aromatic substituted fatty acids are potential candidates for the treatment of neurodegenerative diseases.
  • Fukie Niijima-Yaoita, Masahiro Tsuchiya, Hiroshi Ohtsu, Kazuhiko Yanai ...
    原稿種別: Regular Article
    2012 年 35 巻 1 号 p. 91-97
    発行日: 2012/01/01
    公開日: 2012/01/05
    ジャーナル フリー
    Exercise necessitates a large supply of O2 and nutrients and rapid removal of CO2 and waste products. Histamine is a regulator of the microcirculation (which performs these exchanges), suggesting a possible involvement of histamine in exercise. Histamine is released from either mast cells or non-mast cells. In the latter, histamine is newly formed via the induction of histidine decarboxylase (HDC) in response to an appropriate stimulus, and it is released without being stored. Here, in mice, we examined the role of histamine or HDC induction in exercise. Prolonged walking (PW) (in a cylindrical cage turned electrically) increased HDC mRNA and HDC activity in quadriceps femoris muscles. Mice given a histamine H1-receptor antagonist [fexofenadine (peripherally acting) or pyrilamine (peripherally and centrally acting)] or an irreversible HDC inhibitor (α-fluoromethylhistidine) displayed less PW endurance than control mice. Ranitidine (H2-receptor antagonist) tended to reduce endurance. Other histamine-receptor (H3 and H4) antagonists had no significant effects on endurance. Mice deficient in HDC or histamine H1-receptors displayed markedly less endurance than control mice, and HDC activity in the quadriceps femoris of H1-deficient mice was rapidly elevated by PW. Fexofenadine significantly reduced the muscle levels of nitric oxide (NO) metabolites and glycogen after PW. The results support the ideas that (i) histamine is involved in protecting against exercise-induced fatigue or exhaustion, (ii) histamine exerts its protective effect via H1 receptors and the ensuing production of NO in skeletal muscle, and (iii) histamine is provided, at least in part, by HDC induction in skeletal muscles during prolonged exercise.
  • Mi-Yeon Cho, Su-Young Park, Sumin Park, Yong Rok Lee, Gi-dong Han, Jun ...
    原稿種別: Regular Article
    2012 年 35 巻 1 号 p. 98-104
    発行日: 2012/01/01
    公開日: 2012/01/05
    ジャーナル フリー
    Plant-derived polyhenols inhibit cancer cell proliferation and induce apoptosis. Recently, prenylflavonoids and alkyl-phloroacetophenones have been reported for their in vitro antitumor activity. In the present study, we examined the cytotoxic activity of prenyl (3-PAP) and geranyl (3-GAP) derivatives of phloroacetophenone, and xanthohumol (XN), a prenyl-chalcone, in human breast cancer (MCF-7) and human sarcoma (HT1080) cell lines in vitro. 3-GAP showed the strongest cytotoxicity in these cell lines with IC50 values of less than 10 µM. In addition, we report that 3-GAP is a more potent anti-cancer agent for breast cancer than XN which is a well-known anticancer flavonoid. Moreover, 3-GAP did not induce cytotoxicity in the normal cell line, TCMK-1, whereas 3-PAP and XN significantly reduced TCMK-1 cell viability. In 3-GAP-treated MCF-7 cells, nuclear accumulation and transcriptional activity of p53 were increased. In addition, pro-apoptotic Bax but not B-cell lymphoma 2 (Bcl-2) expression was increased by 3-GAP. In accordance with the Bax increase, 3-GAP induced mitochondrial cytochrome c release and activated caspase-9, an initiator of the caspase cascade. In the MCF-7 cell line which does not express caspase-3, activation of caspase-7, a member of the caspase-3 subfamily, was increased by 3-GAP. The present results indicate that synthetic 3-GAP is a safe and effective anti-cancer agent, and the Bax-mediated mitochondrial pathway is the main apoptosis signaling pathway of 3-GAP in MCF-7 cells.
Notes
  • Seog Hyeon Youn, Jin Sun Lee, Myung Sun Lee, Eun Young Cha, Phuong Thi ...
    原稿種別: Note
    2012 年 35 巻 1 号 p. 105-110
    発行日: 2012/01/01
    公開日: 2012/01/05
    ジャーナル フリー
    AMP-activated protein kinase (AMPK) is a sensor of cellular energy status found in all eukaryotes. Recent studies indicate that AMPK activation strongly suppresses cell proliferation in tumor cells, which requires high rates of protein synthesis and de novo fatty acid synthesis for their rapid growth. Pomolic acid (PA) has been previously described as being active in inhibiting the growth of cancer cells. In this study, we investigated PA activated AMPK, and this activity was related to proliferation and apoptosis in MCF7 breast cancer cells. PA inhibited cell proliferation and induced sub-G1 arrest, elevating the mRNA levels of the apoptotic genes p53 and p21. PA activated caspase-3, -9, and poly(ADP-ribose) polymerase, and this effect was inhibited by z-VAD-fmk. AMPK activation was increased by treating cells with PA, inactivated by treating cells with a compound C, and co-treatment consisting of PA and aminoimidazole carboxamide ribonucleotide (AICAR) synergistically activated AMPK. These anti-cancer potentials of PA were accompanied by effects on de novo fatty acid synthesis as shown by the decreased expression of fatty acid synthase, and decreased acetyl-CoA carboxylase activation and incorporation of [3H]acetyl-CoA into fatty acids. In addition, PA inhibited key enzymes involved in protein synthesis such as mammalian target of rapamycin (mTOR), 70 kDa ribosomal protein S6 kinase (p70S6K), and eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1). These results suggest that PA exerts anti-cancer properties through the modulation of AMPK pathways and its value as an anti-cancer agent in breast cancer therapy.
  • Fatema Tuj Zohra, Yoshie Maitani, Toshihiro Akaike
    原稿種別: Note
    2012 年 35 巻 1 号 p. 111-115
    発行日: 2012/01/01
    公開日: 2012/01/05
    ジャーナル フリー
    It was believed for a long time that mRNA is very unstable, and can not be used for therapeutic purposes. In the last decade, however, many research groups proved its transfection feasibility along with advantages and applications. Our investigation is aimed at establishing a potent and efficient mRNA delivery system. We previously reported that an inorganic–organic hybrid carrier by exploiting the advantages of inorganic nano apatite particles onto organic carrier DOTAP {N-[1-(2,3-dioleoloxy)propyl]-N,N,N-trimethyl ammonium chloride} and showed potential effect of carbonate apatite particles on each of the mRNA delivery steps in dividing and non-dividing cell. Here, we report on the development of a more efficient mRNA carrier by complexing ECM protein, fibronectin with the DOTAP-apatite carrier. The carrier showed enhanced uptake of luciferase mRNA both qualitatively and quantitatively. Accelerated cellular endocytosis rate was evaluated using labeled endosome. Finally expression of lucifearse mRNA was higher for fibronectin complexed carrier in compared to the uncoated one.
  • Tohru Yamazaki, Hitomi Okada, Takeshi Sakamoto, Katsuyoshi Sunaga, Tad ...
    原稿種別: Note
    2012 年 35 巻 1 号 p. 116-120
    発行日: 2012/01/01
    公開日: 2012/01/05
    ジャーナル フリー
    The administration of fibrates (fenofibrate, bezafibrate and clofibric acid) to rats induced stearoyl-CoA desaturase (SCD) in the liver, and increased relative expression of mRNAs encoding SCD1 and SCD2 in dose- and time-dependent manners. The magnitudes of the increases in SCD2 mRNA level caused by fenofibrate and clofibric acid were much higher than those of SCD1 at relatively higher doses of the fibrates, and a relatively long time (7 or 14 d) was required for significant induction of SCD2 mRNA expression compared with that of SCD1. Although the absolute number of transcripts for SCD2 was 1,800 times lower than that of SCD1 in the control liver, it was strikingly increased by fibrates. These results suggest that differential regulations operate for the gene expression between SCD1 and SCD2, and that the physiological significance of SCD2 is distinct from that of SCD1 in the liver.
  • Kwang Sik Suh, Seungjoon Oh, Jeong-Taek Woo, Sung-Woon Kim, Jin-Woo Ki ...
    原稿種別: Note
    2012 年 35 巻 1 号 p. 121-126
    発行日: 2012/01/01
    公開日: 2012/01/05
    ジャーナル フリー
    Glucose toxicity contributes to progressive β-cell failure and the development of overt diabetes. Oxidative stress is an important aspect of glucose toxicity in pancreatic β-cells. We investigated whether the flavonoid apigenin protects pancreatic β-cells from 2-deoxy-D-ribose (dRib)-induced oxidative cell damage. HIT-T15 pancreatic β-cells were cultured with or without apigenin in the presence of dRib. Time- and dose-dependent cell viability was monitored using a cell counting kit (CCK-8), while the induction of apoptosis was analyzed using a cell death enzyme-linked immunosorbent assay (ELISA) kit. Mitochondrial membrane potential (ΔΨm) was determined using the JC-1 kit. Intracellular oxidative stress was measured by fluorometric analysis of DCFH oxidation using 2′,7′-dichlorofluorescin diacetate (DCFH-DA) as the probe. In addition, the DNA binding activity of the oxidative stress-related transcriptional factors nuclear factor-κB (NF-κB) and activator protein 1 (AP-1) were analyzed. dRib reduced cell survival and ΔΨm, while it markedly increased intracellular levels of reactive oxygen species (ROS), apoptosis, and the activity of the oxidative stress-related transcription factors NF-κB and AP-1. However, pretreatment of cells with apigenin attenuated all the dRib-induced effects. The anti-oxidants, N-acetyl-L-cysteine (NAC) and alpha lipoic acid (ALA), also prevented both dRib–induced oxidative damage and activation of NF-κB and AP-1. Taken together, these results suggest that apigenin attenuates dRib-induced cell damage in pancreatic β-cells via oxidative stress-related signaling.
  • Seisho Tobinaga, Michio Hashimoto, Iku Utsunomiya, Kyoji Taguchi, Mori ...
    原稿種別: Note
    2012 年 35 巻 1 号 p. 127-129
    発行日: 2012/01/01
    公開日: 2012/01/05
    ジャーナル フリー
    Cardanol (ginkgol) extracted from Ginkgo biloba leaves and cashew nutshell liquid enhances the growth of NSC-34 immortalized motor neuron-like cells and, when chronically administered to young rats, improves working memory-related learning ability as assessed by eight-arm radial maze tasks. These findings suggest that cardanol is one of the components in Ginkgo biloba leaves that improves cognitive learning ability.
feedback
Top