Abstract:
:Prostate cancer (PCA) is the second most malignancy in American men. Advanced stage PCA cells possess unlimited replication potential as well as resistance to apoptosis. Therefore, targeting survival mechanisms and activating apoptotic machinery in PCA cells using nontoxic phytochemicals is suggested as an attractive strategy against this deadly malignancy. In the present study, we assessed the effect of one such botanical agent, namely isosilybin A, on apoptotic machinery and key members of cell survival signaling [Akt, NF-κB, and androgen receptor (AR)] in different PCA cells. Results showed that isosilybin A (90-180 µM) treatment significantly induces apoptotic death by activating both extrinsic (increased level of DR5 and cleaved caspase 8) and intrinsic pathways (caspase 9 and 3 activation) of apoptosis in three different human PCA cell lines namely 22Rv1, LAPC4, and LNCaP. Further, isosilybin A treatment decreased the levels of phospho-Akt (serine-473), total Akt, and the nuclear levels of NF-κB constituents (p50 and p65). Isosilybin A treatment also decreased the AR and PSA level in 22Rv1, LAPC4, and LNCaP cells. Employing pan-caspase inhibitor (Z-VAD.fmk), we confirmed that isosilybin A-mediated decreased AR is independent of caspases activation. Temporal kinetics analysis showed that the primary effect of isosilybin A is on AR, as decrease in AR was evident much earlier (4 h) relative to caspase activation and apoptosis induction (12 h). Overall, our results demonstrated that isosilybin A activates apoptotic machinery in PCA cells via targeting Akt-NF-κB-AR axis; thereby, indicating a promising role for this phytochemical in the management of clinical PCA.
journal_name
Mol Carcinogjournal_title
Molecular carcinogenesisauthors
Deep G,Gangar SC,Oberlies NH,Kroll DJ,Agarwal Rdoi
10.1002/mc.20670subject
Has Abstractpub_date
2010-10-01 00:00:00pages
902-12issue
10eissn
0899-1987issn
1098-2744journal_volume
49pub_type
杂志文章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::Extrachromosomal replication of viral DNA sequences has been observed in transformed as well as in normal cells following "stress"-inducing treatments. To explore the effect of growth conditions on the ability to support such replication, we analyzed SEWA sarcoma cells that grew subcutaneously or as ascites tumors in ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940030506
更新日期:1990-01-01 00:00:00
abstract::Apc mutations cause intestinal tumorigenesis through Tcf4 activation. However, direct techniques for studying Tcf4 activation in vivo are limited. Here, we describe the development of a Tcf4-GFP reporter mouse model for directly studying Tcf4 activation. We first developed a GFP reporter construct (Tcf4-GFP) and trans...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20526
更新日期:2009-09-01 00:00:00
abstract::Thymidylate synthase (TYMS) is involved in the folate metabolism and provision of nucleotides needed for DNA synthesis and repair. Thus, functional genetic variants in TYMS may alter cancer risk. In the study, we evaluated associations of three germline variants (rs2790 A > G, rs16430 6 bp > 0 bp, and rs1059394 C > T)...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22097
更新日期:2015-04-01 00:00:00
abstract::Two genetic instability pathways viz. chromosomal instability, driven primarily by APC mutation induced deregulated Wnt signaling, and microsatellite instability (MSI) caused by mismatch repair (MMR) inactivation, together account for >90% of late-onset colorectal cancer (CRC). Our understanding of early-onset sporadi...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.21976
更新日期:2014-02-01 00:00:00
abstract::Polyamine metabolism is a highly coordinated process that is essential for normal development and neoplastic growth in mammals. Although polyamine metabolism is a validated pathway for prevention of carcinogenesis, the mechanisms by which polyamines elicit their tumorigenic effects are poorly understood. In this study...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22051
更新日期:2014-02-01 00:00:00
abstract::Sel-1-like (SEL1L) is a putative tumor suppressor gene that is significantly downregulated in human pancreatic ductal adenocarcinoma (PDA). The mechanism of the downregulation is unclear. Here, we investigated whether aberrantly upregulated microRNAs (miRNAs) repressed the expression of SEL1L. From reported miRNA micr...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22023
更新日期:2014-09-01 00:00:00
abstract::The expression profile of adenoma induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in A/J mice was compared with that of normal lung tissue by suppression subtractive hybridization (SSH). The mRNAs of surfactant-associated protein A (SP-A) and lysozyme showed characteristically higher transcription in t...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20070
更新日期:2005-02-01 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::In this study, we found that rat nasal coumarin-7-hydroxylase (COH) activity was two orders of magnitude higher than rat hepatic COH activity and could be induced by adding coumarin to the rats' drinking water. In western blot analysis, an anti-cytochrome P450 (Cyp) 2a-5 (mouse liver COH) antibody recognized a sharp b...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940140209
更新日期:1995-10-01 00:00:00
abstract::The Ron receptor tyrosine kinase is overexpressed in approximately half of all human colon cancers. Increased Ron expression positively correlates with tumor progression, and reduction of Ron levels in human colon adenocarcinoma cells reverses their tumorigenic properties. Nearly all colon tumors demonstrate loss of t...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20551
更新日期:2009-11-01 00:00:00
abstract::Matrix metalloproteinases (MMPs) are elevated in patients with squamous cell carcinoma (SCC) over either the head and neck (HNSCC) or the esophagus (ESCC). Synchronous SCC with both HNSCC and ESCC predispose to worse survival. This study tested if serum MMP levels correlate with clinical features and predict survival ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.21874
更新日期:2013-06-01 00:00:00
abstract::Krüppel-like factor 4 (KLF4) is a zinc-finger-containing transcription factor with tumor suppressor activity in various cancer types. Cells that sustain double strand breaks (DSBs) in their DNA due to high levels of reactive oxygen species (ROS) can develop genomic instability, which can result in cancer formation. On...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22161
更新日期:2015-09-01 00:00:00
abstract::Our previous study demonstrated that phosphatidylinositol 3-kinase (PI3K) is necessary for epidermal growth factor (EGF)-induced cell transformation in mouse epidermal JB6 cells. Akt and the mammalian target of rapamycin (mTOR) are regarded as PI3K downstream effectors. Therefore, in this study, we investigated the ro...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.10140
更新日期:2003-09-01 00:00:00
abstract::Malignant rhabdoid tumors (MRTs) are poorly differentiated pediatric cancers that arise in various anatomical locations and have a very poor outcome. The large majority of these malignancies are caused by loss of function of the SNF5/INI1 component of the SWI/SNF chromatin remodeling complex. However, the mechanism of...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20568
更新日期:2009-12-01 00:00:00
abstract::Male F(1) hybrids between MSM mice carrying a deficient p53 allele and BALB/c mice were irradiated with gamma-rays, and 80 thymic lymphomas were obtained, 46 of which developed in mice carrying the deficient p53 allele. Because the Y chromosome contributes little to cellular function, the stability of the Y chromosome...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:
更新日期:1999-11-01 00:00:00
abstract::Estrogen is thought to be an important etiologic agent in endometrial and breast cancers. However, the mechanism or mechanisms by which estrogen acts as a hormonal carcinogen are not well understood. We hypothesize that in response to chronic exposure to estrogens, human endometrial stromal fibroblasts (ESF) produce f...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(sici)1098-2744(199812)23:4<217::aid-mc4>3
更新日期:1998-12-01 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::The most common NF1 feature is the benign neurofibroma, which consists predominantly of Schwann cells. Dermal neurofibromas usually arise during puberty and increase in number throughout adulthood. Plexiform neurofibromas, associated with larger nerves, are often congenital and can be life threatening. Malignant perip...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20236
更新日期:2007-07-01 00:00:00
abstract::The E5 open reading frame (ORF) from bovine papillomavirus type 1 (BPV 1) as well as the E5 ORFs from human papillomaviruses (HPV) type 6 and type 16 have been reported to transform immortalized rodent cells. In an analysis of murine and human tumors for the presence of putative papillomavirus-related sequences, we cl...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940060204
更新日期:1992-01-01 00:00:00
abstract::Urothelial cell carcinoma of the bladder (UCCB) is the most common form of bladder cancer and it is estimated that ~15,000 people in the United States succumbed to this disease in 2013. Bladder cancer treatment options are limited and research to understand the molecular mechanisms of this disease is needed to design ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22319
更新日期:2016-05-01 00:00:00
abstract::The WW domain-containing oxidoreductase (WWOX) gene is an identified tumor suppressor gene, of which several single nucleotide polymorphisms have been reported to contribute to cancer susceptibility. We hypothesized that genetic variations in WWOX are associated with lung cancer risk. In two independent case-control s...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.21934
更新日期:2013-11-01 00:00:00
abstract::The aims of the present study are to investigate sub-cellular location, differential expression in different cancer stages and functional role of FAM134B in colon cancer development. FAM134B expression was studied and quantified at protein and mRNA levels in cell lines using immunocytochemistry, Western blot and real-...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22488
更新日期:2017-01-01 00:00:00
abstract::The levels of the antioxidant enzyme manganese superoxide dismutase (Mn-SOD) are frequently decreased in tumor cells and increased in normal cells upon treatment with ionizing radiation. We studied Mn-SOD at different stages during the neoplastic conversion of radiation-initiated Syrian hamster embryo HDR-3 cells. Mn-...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2744(199612)17:4<175::AID-MC1>3
更新日期:1996-12-01 00:00:00
abstract::Nonmelanoma skin cancers (NMSCs) consist of a variety of tumor types including basal cell carcinoma, squamous cell carcinoma, a variety of hair follicle tumors, and sebaceous gland tumors. Genetic alterations that alter the fate of multipotent stem cells are believed to influence NMSC phenotype. We previously generate...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20617
更新日期:2010-04-01 00:00:00
abstract::Telomerase expression is the hallmark of tumor cells, and activation of this ribonucleoprotein complex may be a rate-limiting or critical step in cellular immortalization and oncogenesis. Fungal immunomodulatory protein, FIP-gts, has been isolated from Ganoderma tsugae. In the present study, we expressed and purified ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20161
更新日期:2006-04-01 00:00:00
abstract::Barrett's metaplasia consists of columnar epithelium that replaces the normal esophageal mucosa in patients with chronic gastroesophageal reflux. Because intestinal-type Barrett's metaplasia is the major risk factor for adenocarcinoma development, understanding the mechanisms that predispose the esophageal mucosa to m...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(sici)1098-2744(199902)24:2<128::aid-mc7>3
更新日期:1999-02-01 00:00:00
abstract::The temporal order of replication of several genes was studied in 10T1/2 cells synchronized by release from confluence-induced arrest of proliferation followed by treatment with 2 micrograms/mL aphidicolin for 24 h. DNA subjected to bromodeoxyuridine substitution for 1- or 2-h intervals spanning the S phase was separa...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940010110
更新日期:1988-01-01 00:00:00
abstract::Inflammation plays a major role in colon carcinogenesis. Endogenously produced specialized proresolving lipid mediators (SPMs) play a central role in inflammation and tissue homeostasis, and have been implicated in carcinogenesis. We studied the associations of plasma levels of two SPMs [lipoxin A4 (LXA4 ) and resolvi...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章,随机对照试验
doi:10.1002/mc.22629
更新日期:2017-08-01 00:00:00
abstract::1-Hydroxyanthraquinone (1-HA), which is present in some herbs, and methylazoxymethanol (MAM) acetate, a metabolite of azoxymethane, show synergistic carcinogenicity in rat colon, and 1-HA induces ulcerative changes with simultaneous severe inflammation of the entire colon. In this study, mutations in Ki-ras (exons 1 a...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940120403
更新日期:1995-04-01 00:00:00