Abstract:
:In this study, we investigated the molecular mechanism of doxorubicin (dxr)-induced cytotoxicity on Jurkat cells - a model cell of human acute lymphoblastic leukemia - under normoxic (20% O2) and hypoxic (5% O2) conditions. Using in-cell western analysis, immunofluorescence, flow cytometry analysis, and biochemical inhibitors, we evaluated several oxidative stress (OS) and cell death markers. It was found that dxr (5-100 μmol/l) induced apoptosis by OS mechanisms involving DNA fragmentation (8-48%), loss of mitochondrial membrane potential (ΔΨm, 33-92%), and H2O2 production (15-42%) under normoxia. In addition, dxr (10 μmol/l) induced activation and/or nuclei translocation of NF-κB (6.6, 1.6-fold increase), p53 (4.3, 3.1 f), c-Jun (9.5, 5.0 f), apoptosis-inducing factor (AIF) (1.9, 3.9 f), caspase-3 (3.7, 1.9 f), overexpression of Parkin (2.1, 1.2 f)/PINK-1 (2.1 f) proteins, and reduced DJ-1 levels by half compared with untreated cells under normoxia, according to immunofluorescence and in-cell western analysis, respectively. In contrast, dxr (10 μmol/l) could not induce apoptosis in Jurkat cells under hypoxia. Effectively, dxr significantly reduced DNA fragmentation (6%), expression levels of cell death (e.g. p53, c-Jun, caspase-3, AIF), and OS (e.g. Parkin) markers, whereas it increased ΔΨm, hypoxia-inducible factor 1-α (HIF-1α, 3.1, 2.3 f), NF-κB (6.8, 2.0 f), and DJ-1 (1.3, 1.0 f) levels. This investigation suggests that dxr might efficiently eliminate acute lymphoblastic leukemia cells by OS-induced apoptosis under normoxic conditions through a minimal completeness of cell death signaling (i.e. mitochondria-caspase-3/AIF-dependent pathways) and through a direct DNA damage process. However, hypoxic conditions may reduce the effectiveness of dxr toxicity.
journal_name
Anticancer Drugsjournal_title
Anti-cancer drugsauthors
Mendivil-Perez M,Velez-Pardo C,Jimenez-Del-Rio Mdoi
10.1097/CAD.0000000000000223subject
Has Abstractpub_date
2015-07-01 00:00:00pages
583-98issue
6eissn
0959-4973issn
1473-5741journal_volume
26pub_type
杂志文章abstract::The primary objective was to determine the optimal doses for gemcitabine (prolonged infusion), liposomal doxorubicin (Myocet) and docetaxel as primary (neoadjuvant) chemotherapy for locally advanced breast cancer. Secondary objectives included evaluation of the safety and efficacy of the regimen. Patients (n=19) with ...
journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1097/00001813-200501000-00003
更新日期:2005-01-01 00:00:00
abstract::High expression of vascular endothelial growth factor (VEGF) in patients with breast cancer has been associated with a poor prognosis, indicating that VEGF could be linked to the efficacy of chemotherapy and radiotherapy. It has also been suggested that radiation resistance is partly due to tumour cell production of a...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e32834ea5b3
更新日期:2012-06-01 00:00:00
abstract::Desmoid tumour/aggressive fibromatosis (DT/AF) is a rare soft-tissue neoplasm that is locally aggressive but does not metastasize. There is no standard systemic treatment for symptomatic patients, although a number of agents are used. Tyrosine kinase inhibitors have recently been reported to show useful activity. We r...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000474
更新日期:2017-04-01 00:00:00
abstract::Lipoplatin, currently under phase III evaluation, is a novel liposomal cisplatin formulation highly effective against cancers. Lipoplatin has eliminated or reduced the systemic toxicity frequently seen for cisplatin. The objective of the present study was to determine whether the cytotoxic effect of lipoplatin is depe...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-200603000-00010
更新日期:2006-03-01 00:00:00
abstract::Protein phosphatase 2A (PP2A) is a new target for platinum (Pt)-based cancer chemotherapeutic agents. A series of novel Pt complexes containing demethylcantharidin, a modified component of a traditional Chinese medicine (TCM), [Pt(C8H8O5)(NH2R)2] 1-5 have been shown to inhibit PP2A both in its purified form and in cel...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/01.cad.0000175586.31940.50
更新日期:2005-09-01 00:00:00
abstract::The in vitro antitumor activity of navelbine (NVB, KW-2307), a newly synthesized vinca alkaloid, was compared with that of adriamycin (ADM) against human breast carcinomas inoculated into nude mice at the maximum tolerated dose (MTD) and clinically equivalent dose (CED). The plasma levels of NVB after intravenous inje...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199412000-00004
更新日期:1994-12-01 00:00:00
abstract::The substituted phenazines XR11576 and XR5944 were originally described as dual topoisomerase-I/II poisons. Subsequent reports, however, indicated that the association of their cytotoxicity with cellular topoisomerases was not clear. We set out to study this further using human tumour cell lines, PEO1 ovarian cancer, ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e328010772f
更新日期:2007-02-01 00:00:00
abstract::Neuroblastoma is one of the most common cancers in infancy, arising from the neuroblasts during embryonic development. This cancer is difficult to treat and resistance to chemotherapy is often found; therefore, clinical trials of novel therapeutic approaches, such as targeted-cancer signaling, could be an alternative ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000478
更新日期:2017-06-01 00:00:00
abstract::Since the early 1990s, mitoxantrone has been used as a chemotherapeutic agent for adjuvant intravesical treatment following transurethral resection of superficial transitional cell carcinomas of the bladder. Although its efficacy as adjuvant intravesical therapy remains questionable and its use has not gained wide acc...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/cad.0b013e3282f421fe
更新日期:2008-03-01 00:00:00
abstract::Lymphocytes regenerated after treatment with a high dose of cyclophosphamide (CY) were characterized in nude mice. Ten days after a single injection of 200 mg/kg CY into nude mice, regenerated spleen cells suppressed in vitro primary and second antibody production against sheep red blood cells. The CY-treated spleen c...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199208000-00018
更新日期:1992-08-01 00:00:00
abstract::The antitumor effects of a polyamine biosynthetic pathway inhibitor methylglyoxal bis(cyclopentylamidinohydrazone) (MGBCP) on the human hepatocellular carcinoma SK-HEP-1 cell line have been investigated. The growth of these cultured hepatocellular carcinoma cells was inhibited by MGBCP in a dose-dependent manner. Sper...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199903000-00012
更新日期:1999-03-01 00:00:00
abstract::Low doses of drugs delivered at close, regular intervals are increasingly being used to manage patients with different neoplasms. Despite the good tolerability, treatment-related adverse events still occur following metronomic protocols. The aim of this study was to retrospectively investigate whether polymorphisms of...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000429
更新日期:2016-11-01 00:00:00
abstract::The CD20 antigen is strongly and stably expressed on cells of the B-cell lineage, but not on stem cells, and is thus an ideal target antigen for antibody therapy of B-cell malignancies. Rituximab is a human-mouse chimeric monoclonal antibody to the CD20 antigen that kills B-cells by a number of different effector mech...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:
更新日期:2001-06-01 00:00:00
abstract::The role and regulation of the c-myc protooncogene in breast and ovarian neoplasms is receiving increased attention. The downregulation of the c-myc protooncogene by 1,25-dihydroxyvitamin D3 (calcitriol), retinoic acid (RA) and dexamethasone (Dex) is closely associated with growth inhibition in leukemic cells. Calcitr...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199304000-00012
更新日期:1993-04-01 00:00:00
abstract::The antitumor effect and tumor levels of 5-fluoro-2'-deoxyuridylate (FdUMP) following oral administration of tetradecyl 2'-deoxy-5-fluoro-5'-uridylate (TT-62) were compared with those attained following intravenous (i.v.) or intraperitoneal (i.p.) administration of 5-fluorouracil (5-FU) or 5-fluoro-2'-deoxyuridine (FU...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199206000-00013
更新日期:1992-06-01 00:00:00
abstract::Chemotherapy for breast cancer is given on the basis of empirical information from clinical trials, an approach which falls to take into account the known heterogeneity of chemosensitivity between patients. Previous attempts to determine chemosensitivity ex vivo have been disappointing, but in this study results from ...
journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章
doi:10.1097/00001813-199608000-00002
更新日期:1996-08-01 00:00:00
abstract::Docetaxel has shown promise for the treatment of hormone-refractory prostate cancer and has become the standard of care. The flare phenomenon is a known entity in androgen-deprivation therapy of advanced prostate cancer and it has also been described in palliative chemotherapy of hormone-refractory prostate cancer. Th...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/01.cad.0000231468.69535.97
更新日期:2006-09-01 00:00:00
abstract::beta-Lapachone is a naturally occurring quinone obtained from the bark of the lapacho tree (Tabebuia avellanedae) with cancer chemopreventive properties. The objective of the present study was to investigate the effect of beta-lapachone on the cell growth and apoptosis in human colon carcinoma tumor cell line HCT-116....
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-200311000-00011
更新日期:2003-11-01 00:00:00
abstract::This study aims to explore the effect and mechanism of pyruvate kinase M2 (PKM2) on chemotherapy resistance of estrogen receptor-positive breast cancer (ER BC) by regulating aerobic glycolysis. The expression of PKM2 in ER BC MCF-7 cells, T47D cells and MCF-7/ADR cells (which are subject to adriamycin/ADR induction) w...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000624
更新日期:2018-08-01 00:00:00
abstract::The effect of association of hyperthermia with the anti-inflammatory drug rhein (RH), 4,5-dihydroxyanthraquinone-2-carboxylic acid, on the clonogenic activity of human glioma cells has been examined. RH inhibits neoplastic growth mainly through an ATP depletion, but thermal cell killing is not mediated by the drug-ind...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199208000-00015
更新日期:1992-08-01 00:00:00
abstract::We have previously shown that L-methionine inhibits proliferation of breast, prostate, and colon cancer cells. This study extends these findings to BXPC-3 (mutated p53) and HPAC (wild-type p53) pancreatic cancer cells and explores the reversibility of these effects. Cells were exposed to L-methionine (5 mg/ml) for 7 d...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000038
更新日期:2014-02-01 00:00:00
abstract::We have examined the biological activity of keto-C-glycosides (KCGs), a new family of drugs displaying antiproliferative and cytotoxic properties on tumor cells. KCG1, the most powerful drug tested on epithelial derived neoplastic cells, was 25-125 times more cytostatic on epithelial cells than on lymphoma. By contras...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199208000-00006
更新日期:1992-08-01 00:00:00
abstract::The presence of DNA fragments circulating in cancer patients was described a number of years ago. The mere presence of DNA in the circulation is not indicative of cancer. However, there are reports that apoptosis and necrosis of the cancer cells can increase the levels of circulating DNA. The study of plasma DNA with ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/00001813-200204000-00003
更新日期:2002-04-01 00:00:00
abstract::The aim of this review is to summarize currently available information on the rapid screening and initial characterization of the different mechanisms of resistance to hydrophilic [e.g. methotrexate (MTX)] and lipophilic antifolates [e.g. trimetrexate (TMTX)] in cultured mammalian cells using fluorescein-methotrexate ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/00001813-199310000-00002
更新日期:1993-10-01 00:00:00
abstract::In our institution, 103 glioblastoma multiforme (GBM) patients aged from 55 to 83 years were treated since November 1994 as follows. All patients underwent surgical intervention (gross total resection, n = 35; subtotal resection, n = 38; stereotactic biopsy, n = 30). Subsequently all patients were offered radiotherapy...
journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章
doi:10.1097/00001813-200302000-00007
更新日期:2003-02-01 00:00:00
abstract::Heavy water (deuterium oxide: D2O) contains a neutron and a proton in its hydrogen atoms and shows a variety of biologic activities different from normal light water. In the present study the cytotoxic and cytostatic activity of D2O was assessed using a BALB/c-3T3 fibroblast cell line and four human digestive organ ca...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199809000-00007
更新日期:1998-09-01 00:00:00
abstract::We evaluated economic implications of treatment with irinotecan, following a RCT which demonstrated significantly increased survival at 1 year with irinotecan (45%) compared to infusional 5-fluorouracil (5-FU) (32%) in patients with metastatic colorectal cancer. Medical care consumption data were collected prospective...
journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00001813-199907000-00014
更新日期:1999-07-01 00:00:00
abstract::The ONYX-015 virus is a mutated adenovirus that in theory selectively replicates and induces cytolysis in tumor cells lacking functional p53. The present study investigated whether ONYX-015 viral infection alone or in combination with conventional chemotherapeutic agents could significantly increase apoptosis in human...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:
更新日期:2002-01-01 00:00:00
abstract::Preoperative chemoradiotherapy (CRT) is generally performed for locally advanced rectal cancer (LARC, cStage 2 or 3) to improve local disease control and patient survival. The pathological tumor response to CRT is a surrogate marker that is associated with oncological outcome. Thus, markers that predict the response t...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000391
更新日期:2016-09-01 00:00:00
abstract::Cancer stem cells play a fundamental role in the growth, metastasis, recurrence, and chemoresistance of cancers of various origins; therefore, targeting these cells may prospectively help to eradicate cancer cells from patients. In this study, the effect of tetrandrine on the proliferation of CD133-positive (CD133) He...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000803
更新日期:2019-10-01 00:00:00