Abstract:
:Aerobic glycolysis is an established hallmark of cancer. Neoplastic cells display increased glucose consumption and a corresponding increase in lactate production compared to the normal cells. Aerobic glycolysis is regulated by the phosphatidylinositol-3-kinase (PI3K)/Akt/ mammalian target of rapamycin (mTOR) signaling pathway, as well as by oncogenic transcription factors such as c-Myc and hypoxia inducible factor 1α (HIF-1α). γ-Tocotrienol is a natural isoform within the vitamin E family of compounds that displays potent antiproliferative and apoptotic activity against a wide range of cancer cell types at treatment doses that have little or no effect on normal cell viability. Studies were conducted to determine the effects of γ-tocotrienol on aerobic glycolysis in mouse +SA and human MCF-7 breast cancer cells. Treatment with γ-tocotrienol resulted in a dose-responsive inhibition of both +SA and MCF-7 mammary tumor cell growth, and induced a relatively large reduction in glucose utilization, intracellular ATP production and extracellular lactate excretion. These effects were also associated with a large decrease in enzyme expression levels involved in regulating aerobic glycolysis, including hexokinase-II, phosphofructokinase, pyruvate kinase M2, and lactate dehydrogenase A. γ-Tocotrienol treatment was also associated with a corresponding reduction in the levels of phosphorylated (active) Akt, phosphorylated (active) mTOR, and c-Myc, but not HIF-1α or glucose transporter 1 (GLUT-1). In summary, these findings demonstrate that the antiproliferative effects of γ-tocotrienol are mediated, at least in the part, by the concurrent inhibition of Akt/mTOR signaling, c-Myc expression and aerobic glycolysis.
journal_name
Biol Pharm Bulljournal_title
Biological & pharmaceutical bulletinauthors
Parajuli P,Tiwari RV,Sylvester PWdoi
10.1248/bpb.b15-00306subject
Has Abstractpub_date
2015-01-01 00:00:00pages
1352-60issue
9eissn
0918-6158issn
1347-5215journal_volume
38pub_type
杂志文章abstract::Tryptanthrin originally isolated from Isatis tinctoria L. has been characterized to have anti-inflammatory activities through the dual inhibition of cyclooxygenase-2 and 5-lipoxygenase mediated prostaglandin and leukotriene syntheses. To characterize phase I metabolite(s), tryptanthrin was incubated with rat liver mic...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.30.1991
更新日期:2007-10-01 00:00:00
abstract::Panaxydol, a polyacetylenic compound derived from Panax ginseng has been reported to suppress the growth of cancer cells. However, the molecular mechanisms underlying cell cycle arrest by this compound in non-small cell lung cancer (NSCLC) are unknown. Our study found that panaxydol treatment induced cell cycle arrest...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.b18-00447
更新日期:2018-01-01 00:00:00
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journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
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更新日期:2015-01-01 00:00:00
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journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.32.1819
更新日期:2009-11-01 00:00:00
abstract::CCAAT/enhancer-binding protein delta (C/EBPdelta) transcription factor is rapidly induced at an early stage of acute phase response. We previously reported that this induction was mainly mediated by acute phase response factor/signal transducers and activators of transcription 3 (APRF/STAT3). Furthermore, the high exp...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.23.1424
更新日期:2000-12-01 00:00:00
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journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章,评审
doi:10.1248/bpb.b13-00014
更新日期:2013-01-01 00:00:00
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journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.b16-00140
更新日期:2016-01-01 00:00:00
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journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.17.871
更新日期:1994-06-01 00:00:00
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journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.20.288
更新日期:1997-03-01 00:00:00
abstract::DJ-927, currently undergoing Phase I clinical trial, is a new orally effective taxane with potent antitumor effects. The absorption, tissue distribution, and excretion of DJ-927 were investigated in mice, dogs, and monkeys after a single oral administration. After oral administration of [14C]DJ-927, radioactivity was ...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.27.345
更新日期:2004-03-01 00:00:00
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journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.26.368
更新日期:2003-03-01 00:00:00
abstract::Mouse thioglycollate-induced peritoneal macrophages effectively, in the absence of serum, recognized mouse polymorphonuclear leukocytes (PMNs) mildly oxidized with diamide, superoxide (hypoxanthine/xanthine oxidase) or t-butyhydroperoxide, or modified with N-ethylmaleimide (NEM). The recognition reached a maximum when...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.24.19
更新日期:2001-01-01 00:00:00
abstract::Checkpoint kinase 1 (Chk1) plays important roles in genotoxic stress-induced cell cycle checkpoint and in normal cell cycle progression. Here, we show that Chk1 is cleaved in the treatment of apoptotic dose of etoposide (ETP) or cisplatin (CIS) but not of viable dose in HeLa S3 cells. The cleavage of Chk1 was complete...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.30.359
更新日期:2007-02-01 00:00:00
abstract::Selective inhibitors of phosphodiesterases (PDEs) have been suggested to have anti-inflammatory effects on bronchial asthma through the inhibition of chemotaxis, adhesion, degranulation, the respiratory burst, and survival prolongation of eosinophils. However, the mechanisms by which these agents inhibit eosinophil su...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.28.515
更新日期:2005-03-01 00:00:00
abstract::Here, we confirmed that stable expression of B-cell lymphoma-xL (Bcl-xL) in N18TG neuroglioma cells could suppress c-Jun N-terminal protein kinase (JNK) activation, nuclear fragmentation, and cell death caused by etoposide treatment. Moreover, additional overexpression of JNK1 led to partially antagonize the antiapopt...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.31.1686
更新日期:2008-09-01 00:00:00
abstract::Cloning of polyketide synthase (PKS) gene for amphidinolide biosynthesis was attempted from a dinoflagellate Amphidinium sp. (strain Y-42). Fourteen beta-ketoacyl synthase gene fragments were obtained by Polymerase Chain Reaction (PCR) amplification from degenerated primer sets designed on the basis of the conserved a...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.29.1314
更新日期:2006-07-01 00:00:00
abstract::Granisetron (GRN) is widely used for patients with various cancers who suffer from chemotherapy-induced vomiting and nausea. The, pharmacokinetics of GRN has not been fully evaluated in such patients, however, and its dosage regimen is still controversial. In this study, we determined GRN levels in serum and urine fro...
journal_title:Biological & pharmaceutical bulletin
pub_type: 临床试验,杂志文章
doi:10.1248/bpb.24.432
更新日期:2001-04-01 00:00:00
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journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.b12-00057
更新日期:2012-01-01 00:00:00
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journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
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更新日期:2005-02-01 00:00:00
abstract::In the present study, we investigated the neuroprotective effects of kaempferol in the mouse model of Parkinson's disease, which was induced by neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We confirmed that MPTP led to behavioral deficits, depletion of dopamine and its metabolites, reduction in supe...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.34.1291
更新日期:2011-01-01 00:00:00
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journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.b16-00828
更新日期:2017-01-01 00:00:00
abstract::Morinda citrifolia L., known as noni, originated from Indonesia exhibits various pharmacological activities including anti-inflammatory properties. However, the validity of noni fruit juice as a treatment for rheumatoid arthritis (RA), an autoimmune disorder, has not been confirmed yet. Therefore, the main purpose of ...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.b18-00480
更新日期:2019-01-01 00:00:00
abstract::The effect of gel-forming (1-->3)-beta-D-glucan on the immunological activities of murine kupffer cells was examined. A branched type gel-forming (1-->3)-beta-D-glucan, GRN, was administered intravenously to mice. GRN associating to kupffer cells was detected by an immunohistochemical technique using anti-GRN antibody...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.21.278
更新日期:1998-03-01 00:00:00
abstract::Cytochrome P450 monooxygenases (P450s) catalyze a wide variety of monooxygenation reactions in primary and secondary metabolism in plants. The share of P450 genes in each plant genome is estimated to be up to 1%. This implies that the diversification of P450 has made a significant contribution to the ability to acquir...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章,评审
doi:10.1248/bpb.35.824
更新日期:2012-01-01 00:00:00
abstract::We previously reported the isolation of a novel cerebroside (1-O-(beta-D-glucopyranosyl)-(2S,3R,4E,8Z)-2-N-palmityloc tadecasphinga-4,8-diene; LCC) from the fruits of Lycium chinense MILL. (Solanaceae) which protected primary cultured rat hepatocytes from the toxicity induced by carbon tetrachloride (CCl4). The presen...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.22.873
更新日期:1999-08-01 00:00:00
abstract::The roles of OmpC and OmpF in acidic resistance (AR) were examined. When ompC and ompF were deleted, AR was decreased. The decreased level of AR seen in the mutant that was deficient in ompC and ompF was elevated by the addition of glutamate, but not by the addition of arginine or lysine. The expression levels of adiA...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.34.330
更新日期:2011-01-01 00:00:00
abstract::The anti-herpes simplex virus type 1 (HSV-1) activity of 15 oleanan-type triterpenoides including glycyrrhizin and its sapogenol was examined and their structure-activity relationships were discussed. Although glycyrrhizin which exhibited in vivo efficacy against HSV-1 replication showed moderate in vitro anti-HSV-1 a...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.28.1779
更新日期:2005-09-01 00:00:00
abstract::In order to treat a hyperammonemic patient with adult-onset type-II citrullinemia (CTLN2), sodium phenylacetate powder was prepared from chemical reagent grade phenylacetic acid in Gunma University Hospital. After purification by recrystalization, phenylacetic acid was neutralized with sodium carbonate and dried at 70...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.25.1244
更新日期:2002-09-01 00:00:00
abstract::Studies were performed to characterize the opioid receptors in guinea pig brain using the radiolabeled opioid antagonists, [3H]naloxone and [3H]diprenorphine and the kappa-agonist [3H]U-69593. The binding of [3H]U-69593 to guinea pig cerebellar membranes was reduced by NaCl, guanyl-5'yl-imidodiphosphate (GppNHp) and N...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.16.921
更新日期:1993-09-01 00:00:00
abstract::Uridine diphosphate (UDP)-glucuronosyltransferase 1A1 (UGT1A1) plays important roles in the glucuronidation of various drugs and endogenous substances. Minipigs have been used as experimental animals in pharmacological and toxicological studies, because many of their physiological characteristics are similar to those ...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.b12-00986
更新日期:2013-01-01 00:00:00