Abstract:
:Aurora-B kinase overexpression plays important roles in the malignant progression of prostate cancer (PCa). AZD1152-HQPA, as an inhibitor of Aurora-B, has recently emerged as a promising agent for cancer treatment. In this study, we aimed to investigate the effects of AZD1152-HQPA on reactive oxygen species (ROS) generation and mitochondrial function in PCa. We used AZD1152-HQPA (Barasertib), a highly potent and selective inhibitor of Aurora-B kinase. The effects of AZD1152-HQPA on cell viability, DNA content, cell morphology, and ROS production were studied in the androgen-independent PC-3 PCa cell line. Moreover, the mitochondrial copy number and the expression of genes involved in cell survival and cancer stem cell maintenance were investigated. We found that AZD1152-HQPA treatment induced defective cell survival, polyploidy, micronuclei formation, cell enlargement, and cell death by significant overexpression of p73, p21 and downregulation of cell cycle-regulatory genes in a drug concentration-dependent manner. Moreover, AZD1152 treatment led to an excessive ROS generation and an increase in the mitochondrial copy number not only in PC-3 but also in several other malignant cells. AZD1152 treatment also led to downregulation of genes involved in the maintenance of cancer stem cells. Our results showed a functional relationship between the aurora kinase inhibition, an increase in mitochondrial copy number, and ROS generation in therapeutic modalities of cancer. This study suggests that the excessive ROS generation may be a novel mechanism of cytotoxicity induced by the aurora kinase inhibitor, AZD1152-HQPA.
journal_name
Anticancer Drugsjournal_title
Anti-cancer drugsauthors
Zekri A,Mesbahi Y,Ghanizadeh-Vesali S,Alimoghaddam K,Ghavamzadeh A,Ghaffari SHdoi
10.1097/CAD.0000000000000523subject
Has Abstractpub_date
2017-09-01 00:00:00pages
841-851issue
8eissn
0959-4973issn
1473-5741journal_volume
28pub_type
杂志文章abstract::The beta-carboline alkaloids are naturally existing plant substances. It is known that these alkaloids have a wide spectrum of neuropharmacological, psychopharmacological, and antitumor effects. Therefore, they have been traditionally used in oriental medicine for the treatment of various diseases including cancers an...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e32832a2dd9
更新日期:2009-06-01 00:00:00
abstract::Declopramide (3-chloroprocainamide) has been identified in previous studies as a representative of a new class of chemosensitizers. In this study, the toxicity and pharmacokinetics of declopramide have been investigated and compared with a structural analog, metoclopramide (MCA). Declopramide has not induced central n...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199901000-00010
更新日期:1999-01-01 00:00:00
abstract::Patients with metastatic squamous cell cancer of the head and neck (SCCHN) have a poor prognosis, with most patients surviving less than a year. Immunotherapy (IO) is changing the natural history of the disease and programmed death-ligand 1 (PD-L1) inhibitors are showing notable improvements in survival with a more fa...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000706
更新日期:2019-02-01 00:00:00
abstract::The array of tools currently available and the aim of treatment make choosing the best therapeutic strategy in metastatic colorectal cancer (CRC) an increasing challenge worldwide. We present the case of a 53-year-old man with metachronous metastases (liver-only metastatic disease) treated with FOLFOXIRI as first-line...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000761
更新日期:2019-04-01 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::To devise a meaningful nutritional therapy in cancer, a greater understanding of nutritional dimensions as well as of expectations of patients and disease impact is essential. We have shown that nutritional deterioration in patients with gastrointestinal and head and neck cancer was multifactorial and mainly determine...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/CAD.0b013e328345b4c5
更新日期:2011-08-01 00:00:00
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journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/00001813-200207000-00001
更新日期:2002-07-01 00:00:00
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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::A toxicology study of DENSPM was carried out in rats by multiple (once daily for 5 days) intravenous injection. Doses of 12.5, 25 and 50 mg DENSPM/kg were well tolerated. Infusion of 100 mg DENSPM resulted in distressing physical signs, including labored breathing, convulsive movements and acute death. There were no e...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199408000-00010
更新日期:1994-08-01 00:00:00
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journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/00001813-199601001-00003
更新日期:1996-01-01 00:00:00
abstract::A cost-utility analysis has been performed comparing taxanes, vinorelbine and standard therapy for metastatic breast cancer considering clinical efficacy, quality-adjusted-life-years (QALYs) and costs. A decision model has been built. Clinical efficacy data were collected by literature review. Utility data and cost da...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-200107000-00007
更新日期:2001-07-01 00:00:00
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journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章
doi:10.1097/00001813-200202000-00009
更新日期:2002-02-01 00:00:00
abstract::Glucocorticosteroids (GC) play an important role in the treatment of neuro-oncologic patients. GC are used for the management of malignant brain tumors, either primary of secondary, neoplastic epidural spinal cord compression (NESC), as adjuvant chemotherapy of some central nervous system tumors and perioperatively in...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/00001813-199502000-00002
更新日期:1995-02-01 00:00:00
abstract::The extravasation of chemotherapeutic agents is a challenge for oncologic care teams. The management of nonliposomal (conventional) anthracyclines is well established in clinical practice guidelines, including general measures and specific antidotes, such as dexrazoxane. However, there is little scientific evidence on...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/CAD.0000000000000672
更新日期:2018-10-01 00:00:00
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journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e3282a213ce
更新日期:2007-11-01 00:00:00
abstract::In a retrospective study, we calculated the treatment and follow-up costs of patients with newly diagnosed multiple myeloma. The total treatment programme consisted of eight phases: VAD or VAMP chemotherapy, follow-up I, high-dose melphalan followed by transplantation of whole blood, follow-up II, collection of periph...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199811000-00008
更新日期:1998-11-01 00:00:00
abstract::The recombinant monoclonal antibody trastuzumab has antiproliferative effect on breast cancer (BC) cells with ErbB2 overexpression. We postulated that a mechanism able to modify ErbB2 expression enhances the antitumor effect of trastuzumab. We analyzed whether granulocyte-colony stimulating factor (G-CSF), widely used...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e3283050083
更新日期:2008-08-01 00:00:00
abstract::Genome profiling approaches such as cDNA microarray analysis and quantitative reverse transcription polymerase chain reaction are playing ever-increasing roles in the classification of human cancers and in the discovery of biomarkers for the prediction of prognosis in cancer patients. Increasing research efforts are a...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/CAD.0b013e3280262427
更新日期:2007-06-01 00:00:00
abstract::Non-resectable biliary tract cancer is associated with poor prognosis due to widespread resistance to chemotherapeutic agents and radiotherapy. It is therefore essential to explore new therapeutic approaches like the inhibition of tyrosine kinases. The aim of this study was to determine the expression of c-kit and pla...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-200310000-00011
更新日期:2003-10-01 00:00:00
abstract::Electrochemotherapy using intratumoral cisplatin administration was tested on EAT tumors in mice. Mice were treated with eight electric pulses (100 micros, 1 Hz, 1040 V) and/or cisplatin (1, 2, 4 and 8 mg/kg). Cisplatin treatment resulted in up to 20 days of tumor growth delay. Electrochemotherapy resulted in tumor cu...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199807000-00002
更新日期:1998-07-01 00:00:00
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journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199802000-00005
更新日期:1998-02-01 00:00:00
abstract::CHS 828, a pyridyl cyanoguanidine, is a new drug candidate now in phase I/II trials, that has shown promising anticancer activity in experimental tumor models and primary cultures of cancer cells from patients. In this study the fluorometric microculture cytotoxicity assay was used for evaluation of CHS 828 in primary...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-200208000-00008
更新日期:2002-08-01 00:00:00
abstract::Para-toluenesulfonamide (PTS) has been implicated with anticancer effects against a variety of tumors. In the present study, we investigated the inhibitory effects of PTS on tongue squamous cell carcinoma (Tca-8113) and explored the lysosomal and mitochondrial changes after PTS treatment in vitro. High-performance liq...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000283
更新日期:2015-11-01 00:00:00
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journal_title:Anti-cancer drugs
pub_type:
doi:10.1097/CAD.0b013e3282f2c938
更新日期:2008-02-01 00:00:00
abstract::Organotypic cultures of human A549 cells were used as a tumor model to investigate sequence effects for combination treatments with adriamycin (ADR) and X-irradiation. Initial drug exposure led to the greatest cytotoxic effect especially when X-rays were delivered 24 h later and this subsequent irradiation did not sig...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199204000-00010
更新日期:1992-04-01 00:00:00
abstract::Patients with advanced gastric cancer unresponsive or progressing after PELF chemotherapy (5-fluorouracil, leucovorin, cisplatin and epidoxorubicin) received paclitaxel at the dose of 225 mg/m2 every 3 weeks, over 3 h infusion. Thirty-six patients entered the study, and all of them were evaluable for response and toxi...
journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章
doi:10.1097/00001813-199804000-00003
更新日期:1998-04-01 00:00:00
abstract::To compare the mechanical and chemical properties of three commercially available microspheres loaded with irinotecan. LifePearl (200 µm), DC Bead (100-300 µm), and Tandem (100 µm) microspheres were loaded with irinotecan. For loading, elution, and stability determinations, irinotecan concentrations were quantified us...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000408
更新日期:2016-10-01 00:00:00
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journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/CAD.0000000000000814
更新日期:2019-10-01 00:00:00
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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::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