Molecular evidences for the chemosensitizing efficacy of liposomal curcumin in paclitaxel chemotherapy in mouse models of cervical cancer.


:The microtubule-targeting antineoplastic agent, paclitaxel, is highly efficacious against a wide spectrum of human cancers. However, dose-limiting toxicity and development of drug resistance limit its clinical application. Development of novel strategies that overcome chemoresistance and sensitize cancer cells to paclitaxel can enhance the therapeutic effect of this drug. We have previously shown that curcumin, a natural polyphenol, enhances paclitaxel-induced cytotoxicity in vitro through downregulation of nuclear factor (NF)-κB and Akt pathways. This study was undertaken to determine whether this synergism exists in vivo and to elucidate the underlying molecular mechanisms. Mouse cervical multistage squamous cell carcinoma model using 3-methylcholanthrene (3-MC) and a xenograft model of human cervical cancer in nonobese diabetic severe combined immunodeficient (NOD-SCID) mice using HeLa cells were used to evaluate the synergism. We observed that the combined treatment of curcumin and paclitaxel induced a synergestic reduction in the tumor incidence as well as tumor volume of animals compared with the individual treatments of paclitaxel or curcumin, although curcumin alone could not induce any significant effect at the concentration used. The results suggest that a suboptimal concentration of curcumin augments the antitumor action of paclitaxel by downregulating the activation and downstream signaling of antiapoptotic factors and survival signals such as NF-κB, Akt and mitogen-activated protein kinases that have significant roles in proliferation, survival, angiogenesis and metastasis. This study revealed for the first time that 3-MC-induced tumorigenesis in mice is associated with a strong constitutive activation of NF-κB activity. Furthermore, we also observed that pre-exposure of carcinoma cells isolated from 3-MC-induced tumors to curcumin potentiates paclitaxel-induced apoptosis. Overall, the findings of this preclinical study provide a strong rationale for the validation of this combination through clinical trials. As curcumin could effectively downregulate all these survival signals induced by paclitaxel, we suggest it as a potent chemosensitizer to improve the therapeutic index of paclitaxel.






Sreekanth CN,Bava SV,Sreekumar E,Anto RJ




Has Abstract


2011-07-14 00:00:00
















  • 1q gain and CDT2 overexpression underlie an aggressive and highly proliferative form of Ewing sarcoma.

    abstract::Despite extensive characterization of the role of the EWS-ETS fusions, little is known about secondary genetic alterations and their clinical contribution to Ewing sarcoma (ES). It has been demonstrated that the molecular structure of EWS-ETS lacks prognostic value. Moreover, CDKN2A deletion and TP53 mutation, despite...


    pub_type: 杂志文章


    authors: Mackintosh C,Ordóñez JL,García-Domínguez DJ,Sevillano V,Llombart-Bosch A,Szuhai K,Scotlandi K,Alberghini M,Sciot R,Sinnaeve F,Hogendoorn PC,Picci P,Knuutila S,Dirksen U,Debiec-Rychter M,Schaefer KL,de Álava E

    更新日期:2012-03-08 00:00:00

  • Regulation of Axl receptor tyrosine kinase expression by miR-34a and miR-199a/b in solid cancer.

    abstract::Axl is a receptor that induces proliferation, migration and invasion in cancer. In this study, we show that specific microRNAs (miRNAs) target the 3'-UTR of Axl. Luciferase-reporter assays with wild-type and deleted miR-34 and miR-199a/b seed sequences of Axl 3'-UTR confirmed the specificity of targeting. An inverse c...


    pub_type: 杂志文章


    authors: Mudduluru G,Ceppi P,Kumarswamy R,Scagliotti GV,Papotti M,Allgayer H

    更新日期:2011-06-23 00:00:00

  • HPV E2, E4, E5 drive alternative carcinogenic pathways in HPV positive cancers.

    abstract::The dominant paradigm for HPV carcinogenesis includes integration into the host genome followed by expression of E6 and E7 (E6/E7). We explored an alternative carcinogenic pathway characterized by episomal E2, E4, and E5 (E2/E4/E5) expression. Half of HPV positive cervical and pharyngeal cancers comprised a subtype wi...


    pub_type: 杂志文章


    authors: Ren S,Gaykalova DA,Guo T,Favorov AV,Fertig EJ,Tamayo P,Callejas-Valera JL,Allevato M,Gilardi M,Santos J,Fukusumi T,Sakai A,Ando M,Sadat S,Liu C,Xu G,Fisch KM,Wang Z,Molinolo AA,Gutkind JS,Ideker T,Koch WM,Cali

    更新日期:2020-10-01 00:00:00

  • Ras-MAP kinase signaling by lysophosphatidic acid and other G protein-coupled receptor agonists.

    abstract::Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are extracellular lipid mediators that signal through distinct members of the Edg/LP subfamily of G protein-coupled receptors (GPCRs). LPA and S1P receptors are expressed in almost every cell type and can couple to multiple G proteins (G(i), G(q) and G(12/1...


    pub_type: 杂志文章,评审


    authors: Kranenburg O,Moolenaar WH

    更新日期:2001-03-26 00:00:00

  • The relationship among p53 oligomer formation, structure and transcriptional activity using a comprehensive missense mutation library.

    abstract::Tumor suppressor p53 forms a homo-tetramer through its COOH-terminal oligomerization domain and acts as a sequence-specific transcription factor. We have analysed the interrelation among the transcriptional activities, the structure and the cancer-related mutations in the oligomerization domain by using a comprehensiv...


    pub_type: 杂志文章


    authors: Kawaguchi T,Kato S,Otsuka K,Watanabe G,Kumabe T,Tominaga T,Yoshimoto T,Ishioka C

    更新日期:2005-10-20 00:00:00

  • Src family kinases mediate cytoplasmic retention of activated STAT5 in BCR-ABL-positive cells.

    abstract::Persistent activation of the Abl tyrosine kinase in the BCR-ABL fusion protein is the major cause of chronic myeloid leukemia (CML). Among many other substrates BCR-ABL phosphorylates STAT5 and Src family kinases (SFK). Activated pSTAT5 is essential for initial transformation and maintenance of the disease. Cytokine-i...


    pub_type: 杂志文章


    authors: Chatain N,Ziegler P,Fahrenkamp D,Jost E,Moriggl R,Schmitz-Van de Leur H,Müller-Newen G

    更新日期:2013-08-01 00:00:00

  • Molecular pathology in basal cell cancer with p53 as a genetic marker.

    abstract::Human basal cell cancer (BCC) has unique growth characteristics with virtual inability to metastasize. We investigated clonality and genetic progression using p53 mutations as marker. Sampling was done through microdissection of frozen immunohistochemically stained 16 microm slices of tumors. From 11 BCC tumors 78 sam...


    pub_type: 杂志文章


    authors: Pontén F,Berg C,Ahmadian A,Ren ZP,Nistér M,Lundeberg J,Uhlén M,Pontén J

    更新日期:1997-08-28 00:00:00

  • The proto-oncogene RON is involved in development of epithelial, bone and neuro-endocrine tissues.

    abstract::We previously showed that the proto-oncogene RON encodes the tyrosine kinase receptor for Macrophage Stimulating Protein (MSP), originally isolated as a chemotactic factor for peritoneal macrophages. To elucidate the biological role of MSP we studied the expression of the Ron receptor in vivo, and the response to the ...


    pub_type: 杂志文章


    authors: Gaudino G,Avantaggiato V,Follenzi A,Acampora D,Simeone A,Comoglio PM

    更新日期:1995-12-21 00:00:00

  • Downregulation of stomach cancer-associated protein tyrosine phosphatase-1 (SAP-1) in advanced human hepatocellular carcinoma.

    abstract::SAP-1 (stomach cancer-associated protein tyrosine phosphatase-1) is a transmembrane-type protein tyrosine phosphatase that has been implicated as a negative regulator of integrin-mediated signaling. The potential role of this enzyme in hepatocarcinogenesis has now been investigated by examining its expression in 32 su...


    pub_type: 杂志文章


    authors: Nagano H,Noguchi T,Inagaki K,Yoon S,Matozaki T,Itoh H,Kasuga M,Hayashi Y

    更新日期:2003-07-24 00:00:00

  • Characterization of a third ras gene, rasB, that is expressed throughout the growth and development of Dictyostelium discoideum.

    abstract::Previous reports have indicated that the cellular slime mold Dictyostelium discoideum possesses two ras genes (rasG and rasD) and one rap gene (rap1). All three genes are developmentally regulated, with each showing a different pattern of transcription during the Dictyostelium life cycle. To establish whether there ar...


    pub_type: 杂志文章


    authors: Daniel J,Spiegelman GB,Weeks G

    更新日期:1993-04-01 00:00:00

  • Expression profiling of sodium butyrate (NaB)-treated cells: identification of regulation of genes related to cytokine signaling and cancer metastasis by NaB.

    abstract::Histone deacetylase (HDAC) inhibitors induce growth arrest and apoptosis in a variety of human cancer cells. Sodium butyrate (NaB), a short chain fatty acid, is a HDAC inhibitor and is produced in the colonic lumen as a consequence of microbial degradation of dietary fibers. In order to dissect out the mechanism of Na...


    pub_type: 杂志文章


    authors: Joseph J,Mudduluru G,Antony S,Vashistha S,Ajitkumar P,Somasundaram K

    更新日期:2004-08-19 00:00:00

  • NAD+-dependent deacetylation of H4 lysine 16 by class III HDACs.

    abstract::Histone deacetylases (HDACs) catalyse the removal of acetyl groups from the N-terminal tails of histones. All known HDACs can be categorized into one of four classes (I-IV). The class III HDAC or silencing information regulator 2 (Sir2) family exhibits characteristics consistent with a distinctive role in regulation o...


    pub_type: 杂志文章,评审


    authors: Vaquero A,Sternglanz R,Reinberg D

    更新日期:2007-08-13 00:00:00

  • Structural determinants of the BRCA1 : estrogen receptor interaction.

    abstract::Previously, we showed that the BRCA1 protein interacts directly and functionally with estrogen receptor-alpha (ER-alpha), resulting in the inhibition of estradiol (E2)-stimulated ER-alpha transcriptional activity. The interaction sites were mapped to the N-terminus of BRCA1 (within amino acids (aa) 1-302) and the liga...


    pub_type: 杂志文章


    authors: Ma YX,Tomita Y,Fan S,Wu K,Tong Y,Zhao Z,Song LN,Goldberg ID,Rosen EM

    更新日期:2005-03-10 00:00:00

  • HACS1 encodes a novel SH3-SAM adaptor protein differentially expressed in normal and malignant hematopoietic cells.

    abstract::SH3 and SAM domains are protein interaction motifs that are predominantly seen in signaling molecules, adaptors, and scaffold proteins. We have identified a novel family of putative adaptor genes that includes HACS1. HACS1 encodes a 441 amino acid protein that is differentially expressed in hematopoietic cells and has...


    pub_type: 杂志文章


    authors: Claudio JO,Zhu YX,Benn SJ,Shukla AH,McGlade CJ,Falcioni N,Stewart AK

    更新日期:2001-08-30 00:00:00

  • The Shb signalling scaffold binds to and regulates constitutive signals from the Epstein-Barr virus LMP2A membrane protein.

    abstract::The Epstein-Barr virus latency-associated membrane protein LMP2A has been shown to activate the survival kinase Akt in epithelial and B cells in a phosphoinositide 3-kinase-dependent fashion. In this study, we demonstrate that the signalling scaffold Shb associates through SH2 and PTB domain interactions with phosphor...


    pub_type: 杂志文章


    authors: Matskova LV,Helmstetter C,Ingham RJ,Gish G,Lindholm CK,Ernberg I,Pawson T,Winberg G

    更新日期:2007-07-26 00:00:00

  • Metabolic reprogramming of the tumor.

    abstract::Cancer is classically considered as a genetic and, more recently, epigenetic multistep disease. Despite seminal studies in the 1920s by Warburg showing a characteristic metabolic pattern for tumors, cancer bioenergetics has often been relegated to the backwaters of cancer biology. This review aims to provide a histori...


    pub_type: 历史文章,杂志文章,评审


    authors: Ferreira LM,Hebrant A,Dumont JE

    更新日期:2012-09-06 00:00:00

  • Tumour-suppression function of KLF12 through regulation of anoikis.

    abstract::Suppression of detachment-induced cell death, known as anoikis, is an essential step for cancer metastasis to occur. We report here that expression of KLF12, a member of the Kruppel-like family of transcription factors, is downregulated in lung cancer cell lines that have been selected to grow in the absence of cell a...


    pub_type: 杂志文章


    authors: Godin-Heymann N,Brabetz S,Murillo MM,Saponaro M,Santos CR,Lobley A,East P,Chakravarty P,Matthews N,Kelly G,Jordan S,Castellano E,Downward J

    更新日期:2016-06-23 00:00:00

  • Stem cell programs are retained in human leukemic lymphoblasts.

    abstract::Leukemic lymphoblasts within different immunophenotypic populations possess stem cell properties. However, whether or not the self-renewal program is retained from stem cells or conferred on progenitors by leukemogenic molecules remains unknown. We have addressed the issue in the context of TEL-AML1-associated acute l...


    pub_type: 杂志文章


    authors: Fan D,Zhou X,Li Z,Li ZQ,Duan C,Liu T,Zhang F,Huang Y,Zhang Y,Gao F,Guo Y,Gupta R,Chen G,Enver T,Tang J,Hong D

    更新日期:2015-04-16 00:00:00

  • Human T-cell leukemia virus type 1 (HTLV-1) and leukemic transformation: viral infectivity, Tax, HBZ and therapy.

    abstract::The human T-cell leukemia virus type 1 (HTLV-1) was the first retrovirus discovered to be causative of a human cancer, adult T-cell leukemia. The transforming entity of HTLV-1 has been attributed to the virally-encoded oncoprotein, Tax. Unlike the v-onc proteins encoded by other oncogenic animal retroviruses that tran...


    pub_type: 杂志文章,评审


    authors: Matsuoka M,Jeang KT

    更新日期:2011-03-24 00:00:00

  • The TGF-beta signaling inhibitor Smad7 enhances tumorigenicity in pancreatic cancer.

    abstract::Transforming growth factor-beta (TGF-beta) signaling is dependent on the heterodimerization of the type II TGF-beta receptor (TbetaRII) with the type I TGF-beta receptor (TbetaRI). Activated TbetaRI then mediates TGF-beta signals by inducing the phosphorylation of Smad2 and/or Smad3, which separately hetetorodimerize ...


    pub_type: 杂志文章


    authors: Kleeff J,Ishiwata T,Maruyama H,Friess H,Truong P,Büchler MW,Falb D,Korc M

    更新日期:1999-09-23 00:00:00

  • DNA binding and selective gene induction by different forms of the p53 protein.

    abstract::P53 is a tumor suppressor gene that plays a crucial role in suppressing tumorigenesis by inducing either cell cycle arrest or apoptosis in cells with DNA damage. In more than 50% of tumors p53 is inactivated by gene mutations. However, there have also been reports of tumor cells in which p53 remains wild type and is p...


    pub_type: 杂志文章


    authors: Mayelzadeh F,Martinez JD

    更新日期:2007-05-10 00:00:00

  • Detailed deletion mapping suggests the involvement of a tumor suppressor gene at 17p13.3, distal to p53, in the pathogenesis of lung cancers.

    abstract::The short arm of chromosome 17 is one of the most frequently affected chromosomal regions in lung cancers, while there is solid evidence that the p53 gene at 17p13.1 is a target for frequent 17p deletions. In the present study, we re-evaluated 17p deletions in lung cancers by conducting a detailed analysis of the mini...


    pub_type: 杂志文章


    authors: Konishi H,Takahashi T,Kozaki K,Yatabe Y,Mitsudomi T,Fujii Y,Sugiura T,Matsuda H,Takahashi T,Takahashi T

    更新日期:1998-10-22 00:00:00

  • HPV16 E6 and E7 upregulate the histone lysine demethylase KDM2B through the c-MYC/miR-146a-5p axys.

    abstract::Persistent infection by high-risk human papillomaviruses (HPVs) is associated with the development of cervical cancer and a subset of anogenital and head and neck squamous cell carcinomas. Abnormal expression of cellular microRNAs (miRNAs) plays an important role in the development of cancer, including HPV-related tum...


    pub_type: 杂志文章


    authors: Peta E,Sinigaglia A,Masi G,Di Camillo B,Grassi A,Trevisan M,Messa L,Loregian A,Manfrin E,Brunelli M,Martignoni G,Palù G,Barzon L

    更新日期:2018-03-01 00:00:00

  • Structure of the human LC-PTP (HePTP) gene: similarity in genomic organization within protein-tyrosine phosphatase genes.

    abstract::Recently, various cDNA sequences coding protein-tyrosine phosphatases (PTPs) have been reported and their extensive similarities in the catalytic domains clarified, but knowledge of the structures and organizations of their genes is still limited. In this study, a detailed structure and organization of the human intra...


    pub_type: 杂志文章


    authors: Adachi M,Miyachi T,Sekiya M,Hinoda Y,Yachi A,Imai K

    更新日期:1994-10-01 00:00:00

  • The membrane-anchored MMP-regulator RECK is a target of myogenic regulatory factors.

    abstract::The membrane-anchored MMP-regulator RECK is down regulated in many solid tumors; the extent of RECK down regulation correlates with poor prognosis. Forced expression of RECK in tumor cells results in suppression of angiogenesis, invasion, and metastasis. Studies on the roles and the mechanisms of regulation of the REC...


    pub_type: 杂志文章


    authors: Echizenya M,Kondo S,Takahashi R,Oh J,Kawashima S,Kitayama H,Takahashi C,Noda M

    更新日期:2005-09-01 00:00:00

  • Chromosome end-to-end associations and telomerase activity during cancer progression in human cells after treatment with alpha-particles simulating radon progeny.

    abstract::Chromosome end-to-end associations seen at metaphase involve telomeres and are commonly observed in cells derived from individuals with ataxia telangiectasia and most types of human tumors. The associations may arise because of short telomeres and/or alterations of chromatin structure. There is a growing consensus tha...


    pub_type: 杂志文章


    authors: Pandita TK,Hall EJ,Hei TK,Piatyszek MA,Wright WE,Piao CQ,Pandita RK,Willey JC,Geard CR,Kastan MB,Shay JW

    更新日期:1996-10-03 00:00:00

  • Fibroblast growth factor receptor-1 mediates chemotaxis independently of direct SH2-domain protein binding.

    abstract::Endothelial cells expressing fibroblast growth factor receptor-1 (FGFR-1) migrate and proliferate in response to treatment with FGF. We analysed ligand-induced migration and proliferation of porcine aortic endothelial cells expressing wild-type FGFR-1, point-mutated Y766F FGFR-1, unable to activate phospholipase C-gam...


    pub_type: 杂志文章


    authors: Landgren E,Klint P,Yokote K,Claesson-Welsh L

    更新日期:1998-07-23 00:00:00

  • Selective maternal-allele loss in human lung cancers of the maternally expressed p57KIP2 gene at 11p15.5.

    abstract::Genomic imprinting at 11p15 is suggested to play a role in certain pediatric tumors such as Wilms' tumor, based on the findings of selective maternal loss of this chromosomal region. Although the allele loss at 11p15 is also frequent in a number of cancers of adults including lung, breast, and bladder cancers, possibl...


    pub_type: 杂志文章


    authors: Kondo M,Matsuoka S,Uchida K,Osada H,Nagatake M,Takagi K,Harper JW,Takahashi T,Elledge SJ,Takahashi T

    更新日期:1996-03-21 00:00:00

  • Human oncogenes detected by a defined medium culture assay.

    abstract::Oncogenes in DNAs from human tumor cell lines have been detected by a new transformation assay. Cellular DNAs are transfected into NIH3T3 murine fibroblasts, and transformed cells are selected by maintaining cell cultures in a defined medium lacking platelet-derived or fibroblast growth factors. DNAs from eight of 17 ...


    pub_type: 杂志文章


    authors: Zhan X,Culpepper A,Reddy M,Loveless J,Goldfarb M

    更新日期:1987-01-01 00:00:00

  • Midkine (MDK) growth factor: a key player in cancer progression and a promising therapeutic target.

    abstract::Midkine is a heparin-binding growth factor, originally reported as the product of a retinoic acid-responsive gene during embryogenesis, but currently viewed as a multifaceted factor contributing to both normal tissue homeostasis and disease development. Midkine is abnormally expressed at high levels in various human m...


    pub_type: 杂志文章,评审


    authors: Filippou PS,Karagiannis GS,Constantinidou A

    更新日期:2020-03-01 00:00:00