Abstract:
:We studied the mechanism of the cytotoxic activity of BZL101, an aqueous extract from the herb Scutellaria barbata D. Don, which is currently in phase II clinical trial in patients with advanced breast cancer. The phase I trial showed favorable toxicity profile and promising efficacy. We report here that BZL101 induces cell death in breast cancer cells but not in non-transformed mammary epithelial cells. This selective cytotoxicity is based on strong induction by BZL101 of reactive oxygen species (ROS) in tumor cells. As a consequence, BZL101 treated cancer cells develop extensive oxidative DNA damage and succumb to necrotic death. Data from the expression profiling of cells treated with BZL101 are strongly supportive of a death pathway that involves oxidative stress, DNA damage and activation of death-promoting genes. In breast cancer cells oxidative damage induced by BZL101 leads to the hyperactivation of poly (ADP-ribose) polymerase (PARP), followed by a sustained decrease in levels of NAD and depletion of ATP, neither of which are observed in non-transformed cells. The hyperactivation of PARP is instrumental in the necrotic death program induced by BZL101, because inhibition of PARP results in suppression of necrosis and activation of the apoptotic death program. BZL101 treatment leads to the inhibition of glycolysis selectively in tumor cells, evident from the decrease in the enzymatic activities within the glycolytic pathway and the inhibition of lactate production. Because tumor cells frequently rely on glycolysis for energy production, the observed inhibition of glycolysis is likely a key factor in the energetic collapse and necrotic death that occurs selectively in breast cancer cells. The promising selectivity of BZL101 towards cancer cells is based on metabolic differences between highly glycolytic tumor cells and normal cells.
journal_name
Cancer Biol Therjournal_title
Cancer biology & therapyauthors
Fong S,Shoemaker M,Cadaoas J,Lo A,Liao W,Tagliaferri M,Cohen I,Shtivelman Edoi
10.4161/cbt.7.4.5535subject
Has Abstractpub_date
2008-04-01 00:00:00pages
577-86issue
4eissn
1538-4047issn
1555-8576pii
5535journal_volume
7pub_type
杂志文章abstract::The present studies have examined approaches to suppress MCL-1 function in breast cancer cells, as a means to promote tumor cell death. Treatment of breast cancer cells with CDK inhibitors (flavopiridol; roscovitine) enhanced the lethality of the ERBB1 inhibitor lapatinib in a synergistic fashion. CDK inhibitors inter...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.10.9.13273
更新日期:2010-11-01 00:00:00
abstract::Heat shock proteins (Hsps) modulate several cellular functions and are ubiquitously present in cell. Here, we investigated alterations in the expression of Hsps and explored functional consequences of the same. Moreover, effect of quercetin (Qctn), an inhibitor of Hsps, on chemotherapeutic drugs treatment in hepatoma ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.8.22.9687
更新日期:2009-11-01 00:00:00
abstract::A 67-year-old male presented with anasarca and persistent non-pruritic rash of lower extremities. Physical examination was positive for subcutaneous edema with a non-blanching rash of abdomen and lower extremities. Labs showed leukocytosis, lymphocytosis, anemia and thrombocytopenia. He also had acute kidney injury an...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2017.1394550
更新日期:2018-02-01 00:00:00
abstract::The development of microarray technology has allowed researchers to measure expression levels of thousands of genes simultaneously. Analysis of these data requires the best normalization and statistical approaches to account for the biological and technical variability inherent in the technique. To approach this probl...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.2.4.431
更新日期:2003-07-01 00:00:00
abstract::The F-box protein Fbw7/Sel-10/hCdc4/Ago, which is known to regulate ubiquitination and degradation of numerous important regulators of cell division and death including Notch, cyclin E, c-Jun and c-Myc, has been recently rediscovered as a p53-dependent tumor suppressor. Delineation of the mechanisms of Fbw7 anti-oncog...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.4.5.1703
更新日期:2005-05-01 00:00:00
abstract::Clear cell RCC is the most common, and more likely to metastasize, of the three main histological types of RCC. Pathologic stage is the most important prognostic indicator and nuclear grade can predict outcome within stages of localized RCC. Epithelial tumors are thought to accumulate a series of genetic and epigeneti...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.27314
更新日期:2014-03-01 00:00:00
abstract::Farnesyltransferase inhibitors (FTIs) have been demonstrated to induce growth arrest or apoptosis independent of Ras mutation. Alternatively, Akt has been proposed as a potential target for the FTI's actions. This study investigated whether Lonafarnib was effective in inhibiting the growth of human nonsmall cell lung ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.3.11.1176
更新日期:2004-11-01 00:00:00
abstract::Resistance to apoptosis is one reason for the poor response of malignant brain tumors to therapy. The PPARgamma-modulating drug Troglitazone downregulates the anti-apoptotic FLIP protein and sensitizes glioblastoma cells to apoptosis induced by the death ligand TRAIL. To investigate the molecular basis of an experimen...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.7.12.6966
更新日期:2008-12-01 00:00:00
abstract::Ecto-5'-nucleotidase (CD73) was overexpressed in malignancies of epithelial origin and was involved in a variety of cellular processes such as cytoprotection and anti-inflammation. In the present study, human mammary T-47D cells were transfected with pcDNA-NT5E to establish a CD73 overexpressed cell model. Short small...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.6.3.3762
更新日期:2007-03-01 00:00:00
abstract::Vitamin D derivatives can induce differentiation of human acute myeloid leukemia (AML) cells. Here, we investigated if the G₁ cell cycle block associated with monocytic differentiation is modulated by the p53 status of the cells treated with 1,25D, alone or with plant antioxidants carnosic acid (C) or silibinin (S), a...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.10.4.12366
更新日期:2010-08-15 00:00:00
abstract::Onconase (Onc), a ribonuclease from oocytes or early embryos of Northern Leopard frog (Rana pipiens), is cytostatic and cytotoxic to a variety of tumor lines in vitro, inhibits growth of tumors in animal in vivo models and is currently in Phase IIIb clinical trials for malignant mesothelioma where it displays antitumo...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.7.7.6172
更新日期:2008-07-01 00:00:00
abstract::Taxol (paclitaxel) and Taxotere (docetaxel) are considered as two of the most important anti-cancer chemotherapy drugs. The cytotoxic action of these drugs has been linked to their ability to inhibit microtubule depolymerization, causing growth arrest and subsequent cell death. Studies by a number of laboratories have...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.5.10.3215
更新日期:2006-10-01 00:00:00
abstract::It has been reported that the local introduction of a promoter-less DNA containing the complementary DNA (cDNA) sequence of a gene could induce gene-specific silencing in plants. The feasibility of this kind of silencing in human cancer cells is as yet unknown. The current study was designed to investigate the anti-tu...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.7.10.6586
更新日期:2008-10-01 00:00:00
abstract::Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide, and novel effective drugs against NSCLC are urgently needed. Isodon species are rich in ent-kaurane diterpenoids that have been reported to have antitumor bioactivity. Acetyl-macrocalin B (A-macB) is a novel ent-kaurane diterpen...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2018.1449613
更新日期:2018-07-03 00:00:00
abstract::Interdigitating dendritic cell sarcoma is an extremely rare tumor. The diagnosis is difficult and is based on clinical, pathological and immunohistochemical evaluation. Differential diagnosis includes melanoma, mesenchymal and hematological malignancies. The mainstay of treatment is surgery for limited disease and dif...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.1080/15384047.2015.1057359
更新日期:2015-01-01 00:00:00
abstract::Mcl-1, a pro-survival member of the Bcl-2 protein family, is an attractive target for cancer therapy. We have recently identified the natural product marinopyrrole A (maritoclax) as a novel small molecule Mcl-1 inhibitor. Here, we describe the structure-activity relationship study of pyoluteorin derivatives based on m...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/15384047.2014.972799
更新日期:2014-01-01 00:00:00
abstract:OBJECTIVES:We herein assessed the influence of Epidermal Growth Factor Receptor (EGFR) gene mutations on EGFR expression levels, downstream mediators such as Akt or ERK, and overall survival in patients with ovarian cancer. STUDY DESIGN:EGFR mutation status was analyzed by direct sequencing in 102 Japanese ovarian can...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.11.1.13877
更新日期:2011-01-01 00:00:00
abstract::Chewing tobacco is a common practice in certain socio-economic sections of southern Asia, particularly in the Indian subcontinent and has been well associated with head and neck squamous cell carcinoma. The molecular mechanisms of chewing tobacco which leads to malignancy remains unclear. In large majority of studies,...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2015.1078022
更新日期:2015-01-01 00:00:00
abstract::Tumor formation in immunocompetent hosts is believed to be dependent on the ability of tumor cells to evade the immune system, as suggested by the alterations of expression of the major histocompatibility complex (MHC) and related molecules in a number of cancers. Our previous serial analysis of gene expression (SAGE)...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.3.10.1142
更新日期:2004-10-01 00:00:00
abstract:EXPERIMENTAL DESIGN:To investigate the antitumor effect of sunitinib and FAK/Pyk2 tyrosine kinase inhibitor (PF-562,271)combination therapy in vivo, utilizing human hepatocellular carcinoma (HCC) cells Huh7.5. Nude rats were inoculated subcutaneously with Huh7.5 hepatoma cells. Dosing for Phase 1 was initiated on day 5...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.8.9.8246
更新日期:2009-05-01 00:00:00
abstract::The molecular phenotype of tumor vasculature is different from normal vasculature, offering new opportunities for diagnosis and therapy of cancer, but the identification of tumor-restricted targets remains a challenge. We investigated 13 tumor vascular markers (TVMs) from 50 candidates identified through expression pr...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.12.3.16260
更新日期:2011-08-01 00:00:00
abstract::MDM2 antagonists stabilize and activate wild-type p53, and histone methyltransferase (HMT) inhibitors reduce methylation on histone lysines and arginines. Both MDM2 antagonists and HMT inhibitors are being developed as cancer therapeutics. Wild-type p53 expressing HCT116 colon cancer cells were resistant to apoptosis ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2018.1433500
更新日期:2018-06-03 00:00:00
abstract::Polo-like kinase 1 (Plk1) is a key cell cycle regulator that is frequently overexpressed in human hepatocellular carcinomas. Blockade of the Plk1 pathway has been reported to be capable of inducing anti-tumor effect. Here, plasmids containing U6 promoter-driven shRNAs against human Plk1 were constructed and transfecte...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.11.4.14178
更新日期:2011-02-15 00:00:00
abstract::A number of discoveries have clarified the molecular mechanism of apoptosis, thus clarifying the link between apoptosis and therapeutic outcome. Even though apoptosis is thought to play a major role in anticancer therapy, the clinical relevance of induction of apoptosis remains uncertain, particularly in solid tumors....
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.5.11.3456
更新日期:2006-11-01 00:00:00
abstract:BACKGROUND:IL-24 (interleukin-24) is a promising, multi-functional anti-cancer agent able to selectively induce tumor cell apoptosis while sparing normal cells. Additionally, IL-24 can enhance the immune response to tumors and suppress tumor angiogenesis. In this study, we introduced IL-24 into the oncolytic adenovirus...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.10.3.12308
更新日期:2010-08-01 00:00:00
abstract::Heterotypic hybrids created between dendritic cells (DC) and tumor cells represent an efficient approach for loading DC with tumor-associated antigens (TAA) and DC-tumor hybrid vaccines have shown promising outcomes in various preclinical and clinical studies. Conventional DC-tumor hybrid preparations, however, are un...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.3.11.1217
更新日期:2004-11-01 00:00:00
abstract::Fluids of body cavities result in a series of pathophysiological events associated with non-malignant and malignant conditions that lead to the formation of exudative effusion. Diagnosis of effusion from the patients is frequently troublesome for the cytologist because of the differentiation and biological behavior of...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.4.2.1573
更新日期:2005-02-01 00:00:00
abstract:AIMS:Oral squamous cell carcinoma (OSCC) is the most prevalent malignancy of the oral cavity resulting in severe morbidity and mortality. To date only few proteins have been suggested as potential biomarkers or targets for this type of cancer. Cancerous inhibitor of PP2A (CIP2A) is a protein expressed in epithelial tis...
journal_title:Cancer biology & therapy
pub_type: 评论,杂志文章
doi:10.4161/cbt.10.7.12895
更新日期:2010-10-01 00:00:00
abstract::The greatest health threat from malignant melanoma is death due to metastatic disease. Consequently, the identification of markers predictive of metastatic disease is essential for identifying new therapeutic targets. EphA2, a protein tyrosine kinase receptor commonly expressed in epithelial cells, has been found to b...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.8.3.7485
更新日期:2009-02-01 00:00:00
abstract::Small-molecule inhibitors of cyclin-dependent kinases (CDKs) are known to induce cell cycle arrest and apoptosis in certain cancer cells. In order to evaluate the antitumor activity of one such inhibitor, GW8510, against human lung cancers, we analyzed the effects of GW8510 on six nonsmall cell lung cancer (NSCLC) cel...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.5.2.2316
更新日期:2006-02-01 00:00:00