Abstract:
:Withaferin A (WA), a bioactive constituent of Ayurvedic medicine plant Withania somnifera, is a potent apoptosis inducer in cancer cells but the mechanism of cell death induction is not fully characterized. The present study was undertaken to determine the role of mitogen-activated protein kinases (MAPK), including c-jun NH2 -terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 MAPK, and anti-apoptotic protein myeloid cell leukemia-1 (Mcl-1) in regulation of WA-induced apoptosis using human breast cancer cells. Exposure of MCF-7 (estrogen responsive) and SUM159 (triple negative) human breast cancer cells to WA resulted in increased phosphorylation of ERK, JNK, and p38 MAPK, but these effects were relatively more pronounced in the former cell line than in SUM159. Overexpression of manganese-superoxide dismutase conferred partial protection against WA-mediated hyperphosphorylation of ERK, but not JNK or p38 MAPK. Cell death resulting from WA treatment in MCF-7 cells was significantly augmented by pharmacological inhibition of ERK and p38 MAPK. Interestingly, the WA-induced apoptosis in MCF-7 cells was partially but significantly blocked in the presence of a JNK-specific inhibitor. Pharmacological inhibition of ERK or JNK had no effect on WA-induced apoptosis in SUM159 cells. The WA-treated cells exhibited induction of long and short forms of Mcl-1. RNA interference of Mcl-1 alone triggered apoptosis. Furthermore, the WA-induced cell death in MCF-7 cells was modestly but significantly augmented by knockdown of the Mcl-1 protein. These observations indicate that: MAPK have cell line-specific role in cell death by WA, and Mcl-1 induction confers modest protection against WA-induced apoptosis.
journal_name
Mol Carcinogjournal_title
Molecular carcinogenesisauthors
Hahm ER,Lee J,Singh SVdoi
10.1002/mc.22050subject
Has Abstractpub_date
2014-11-01 00:00:00pages
907-16issue
11eissn
0899-1987issn
1098-2744journal_volume
53pub_type
杂志文章abstract::Although fibroblast growth factor (FGF) signals are strongly associated with malignancy, limited information is available regarding the role of the FGF9 signal in colorectal cancer (CRC). In this study, we investigated the frequency of FGF9 amplification in CRC clinical specimens and the association between the FGF9 g...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22476
更新日期:2017-01-01 00:00:00
abstract::2-Amino-3-methylimidazo[4,5-f]quinoline (IQ), a food carcinogen formed in cooked meats, can induce gene mutation at the hprt locus of CHO-K1 cells in the presence of hepatic S9 mix. To elucidate the molecular nature of IQ-induced mutation, we characterized the entire coding region of the hypoxanthine phosphoribosyl-tr...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940130209
更新日期:1995-06-01 00:00:00
abstract::Alterations in the p16(INK4a) gene have been implicated in the pathogenesis of different human cancers and animal tumors. We postulated that alterations in the p16(INK4a) gene may also be involved in mouse colon tumorigenesis induced by the chemical carcinogen azoxymethane (AOM). In the present study, p16(INK4a) delet...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/1098-2744(200007)28:3<139::aid-mc2>3.0.co;
更新日期:2000-07-01 00:00:00
abstract::To perform a comprehensive genomic analysis of colorectal cancer (CRC) tumor to detect genetic variants and identify novel resistant mutations associated with cetuximab-resistance in CRC patients. A retrospective study was performed using whole exome sequencing (WES) to identify common genetic factors from 22 cetuxima...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.23172
更新日期:2020-05-01 00:00:00
abstract::Deregulation of insulin-like growth factor-1 receptor (IGF-1R) and focal adhesion kinase (FAK) signaling pathways plays an important role in cancer cell proliferation and metastasis. In pancreatic cancer cells, the crosstalk and compensatory mechanisms between these two pathways reduce the efficacy of the treatments t...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20590
更新日期:2010-02-01 00:00:00
abstract::Nuclear factor kappa B (NFkappaB) is a central participant in the metastasis and chemoresistance of colorectal cancer (CRC). However, it is not fully understood to what extent NFkappaB contributes to induction of the metastasis-associated matrix metalloprotease-9 (MMP-9) gene and sensitivity to the commonly used chemo...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20288
更新日期:2007-05-01 00:00:00
abstract::Three okadaic acid class tumor promoters, okadaic acid, dinophysistoxin-1, and calyculin A, have potent tumor-promoting activity in two-stage carcinogenesis experiments on mouse skin. DNA isolated from tumors induced by 7,12-dimethylbenz[a]anthracene (DMBA) and each of these tumor promoters revealed the same mutation ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940020403
更新日期:1989-01-01 00:00:00
abstract::Human DEAD-box RNA helicase gene DDX6 was cloned from B-cell lymphoma cell line RC-K8. Previously, we reported that DDX6 acts as oncogene in several cancers such as colorectal cancer and hepatocellular carcinoma. However, the detailed mechanism of DDX6 action in carcinogenesis is largely unknown. In this study, we exa...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22781
更新日期:2018-05-01 00:00:00
abstract::A rapid and sensitive assay was developed to detect CAA-->AAA mutations at codon 61 of Ha-ras. The region surrounding codon 61 was amplified by the polymerase chain reaction (PCR) using one primer containing a mismatch at the second position of codon 60. Using this primer creates an Msel restriction enzyme site if cod...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940070409
更新日期:1993-01-01 00:00:00
abstract::To determine if hemizygous transgenic mice carrying the human c-Ha-ras gene (CB6F1-Tg Hras2 mice (Hras2 mice)) are susceptible to the carcinogenic potential of known murine carcinogens, male and female Hras2 mice and their non-transgenic CB6F1 littermates (non-Tg mice) were each given a single intraperitoneal injectio...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(sici)1098-2744(199711)20:3<298::aid-mc6>3
更新日期:1997-11-01 00:00:00
abstract::Identification of long noncoding RNA (lncRNA) expression quantitative trait loci (lncR-eQTL) that associated with lung cancer can provide insights into regulatory mechanisms of lncRNA, and help reveal the role of lncRNA in lung cancer. A two-stage case-control design was implemented in this study. We first selected th...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.23013
更新日期:2019-07-01 00:00:00
abstract::Mutations in RB and PTEN are linked to castration resistance and poor prognosis in prostate cancer. Identification of genes that are regulated by these tumor suppressors in a context that recapitulates cancer progression may be beneficial for discovering novel therapeutic targets. Although various genetically engineer...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22444
更新日期:2016-12-01 00:00:00
abstract::BCL2L10 is an apoptosis-related member of the BCL-2 protein family. The role of BCL2L10 in the pathogenesis of hepatocellular carcinoma (HCC) is poorly understood. This study was aimed to investigate the function and underlying mechanisms of BCL2L10 in HCC. BCL2L10 expression in human HCC and corresponding adjacent no...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22580
更新日期:2017-03-01 00:00:00
abstract::PCPH is a gene involved in the regulation of eukaryotic cell proliferation and stress response. Recently, analyses of human and animal solid tumors and cell lines suggested that PCPH protein deregulation may participate in neoplastic progression. To test this possibility, we first examined PCPH expression in several l...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.10091
更新日期:2002-12-01 00:00:00
abstract::Gallbladder carcinoma (GBC) is a highly malignant neoplasm and represents the leading cause of cancer death in Chilean women. In order to determine the potential role of promoter methylation in gallbladder carcinogenesis, we investigated the frequency of this epigenetic mechanism by methylation-specific polymerase cha...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20457
更新日期:2009-01-01 00:00:00
abstract::The majority of ovarian cancers over-express the estrogen receptor (ERα) and grow in response to estrogens. We previously demonstrated that ER induction of the chemokine CXCL12 (stromal cell-derived factor-1) is required for estradiol (E2)-stimulated proliferation of human ovarian carcinoma cells. In the current study...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.21913
更新日期:2013-09-01 00:00:00
abstract::Glucocorticoid hormones are strong inhibitors of normal keratinocyte proliferation, but established mouse skin papillomas and carcinomas become resistant to these hormones. The biological effect of glucocorticoids is mediated through a highly specific glucocorticoid receptor (GR). To study the possible mechanisms of g...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:
更新日期:1997-09-01 00:00:00
abstract::Most human colorectal cancers arise through the accumulation of a series of genetic alterations such as point mutations within the Ki-ras and p53 genes, but the chemical carcinogens that may be implicated in these events are still unidentified. In a previous study, we showed that DNA from human colorectal tissue conta...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2744(199605)16:1<12::AID-MC3>3.
更新日期:1996-05-01 00:00:00
abstract::To analyze the mechanism of neoplastic transformation of rodent diploid cells by ras and myc oncogenes, human EJ c-Ha-ras and mouse c-myc second and third exons promoted by SV40 promoter were connected to pSV2neo and pSV2gpt, respectively. Mouse and rat primary fetal cells cotransfected with both genes formed transfor...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940010404
更新日期:1989-01-01 00:00:00
abstract::Formation of G4 DNA may occur in the course of replication and transcription, and contribute to genomic instability. We have quantitated abundance of G4 motifs and potential for G4 DNA formation of the nontemplate strand of 5' exons and introns of transcripts of human genes. We find that, for all human genes, G4 motif...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20496
更新日期:2009-04-01 00:00:00
abstract::We examined the expression of two groups of matrix metalloproteinases (MMPs), stromelysin and interstitial collagenase, in human skin cancer by northern blot analysis and in situ hybridization. Stromelysin-3 (ST-3) mRNA was overexpressed more than tenfold in 17 of 19 (89%) specimens of basal cell carcinoma (BCC) but i...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940090105
更新日期:1994-01-01 00:00:00
abstract::Ezrin is known to regulate cellular survival, adhesion, migration, and invasion and has been identified as one of the key components of tumor progression and metastasis. The authors investigated ezrin expression in human hepatocellular carcinoma (HCC) and sought to determine its relation with clinicopathologic paramet...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20653
更新日期:2010-09-01 00:00:00
abstract::Using relatively primitive tools in the 1920s, Otto Warburg demonstrated that tumor cells show an increased dependence on glycolysis to meet their energy needs, regardless of whether they were well-oxygenated or not. High rates of glucose uptake, fueling glycolysis, are now used clinically to identify cancer cells. Ho...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章,评审
doi:10.1002/mc.21863
更新日期:2013-05-01 00:00:00
abstract::The adenovirus type 5 (Ad5) 55-kDa E1B oncoprotein has been shown to form complexes with the p53 tumor suppressor protein. These complexes are thought to interfere with normal p53 activity and may be responsible for the paucity of p53 mutations in cells transformed by these viruses. This report describes an example of...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940120102
更新日期:1995-01-01 00:00:00
abstract::Chromosomal double-strand breaks (DSBs) occurring in mammalian cells can initiate genomic instability, and their misrepairs result in chromosomal deletion, amplification, and translocation, common findings in human tumors. The tumor-suppressor protein p53 is involved in maintaining genomic stability. In this study, we...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/1098-2744(200008)28:4<203::aid-mc3>3.0.co;
更新日期:2000-08-01 00:00:00
abstract::Mutations induced by activated benzo[a]pyrene ((+)-anti-B[a]PDE) in Escherichia coli are being investigated, by using both random and adduct-site-specific mutagenesis approaches. A working hypothesis was proposed that the major adduct of (+)-anti-B[a]PDE (formed at N2-Gua) is able to induce different base-substitution...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940130404
更新日期:1995-08-01 00:00:00
abstract::Apigenin (4',5,7-trihydroxyflavone), a flavone subclass of flavonoid widely distributed in many herbs, fruits, and vegetables is a substantial component of the human diet and has been shown to possess a variety of biological activities including tumor growth inhibition and chemoprevention. Recent studies in several bi...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20115
更新日期:2005-09-01 00:00:00
abstract::Recently, tumor initiating cells are considered as the central role of tumorigenicity in hepatocellular carcinoma. Enediyne anticancer antibiotic lidamycin with great potential antitumor activity is currently evaluated in Phase II clinical trials. In this study, we evaluated the effect of lidamycin on tumor initiating...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22069
更新日期:2015-01-01 00:00:00
abstract::The role of telomerase as an essential requirement for the neoplastic conversion of human cells has been controversial. In the model of conversion of normal human cells to cancer cells by the combination of simian virus 40 (SV40) early region genes and oncogenic Ras (H-Ras(G12V)), telomerase (hTERT) was originally des...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20405
更新日期:2008-06-01 00:00:00
abstract::Genotoxicity tests indicate methanol (MeOH) is not mutagenic, but a rodent study has suggested carcinogenic potential, which could result from free radical-initiated oxidative DNA damage. To investigate this possibility we treated male CD-1 mice, New Zealand white rabbits, and cynomolgus monkeys with MeOH (2.0 g/kg ip...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20701
更新日期:2011-03-01 00:00:00