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
















  • Preferential selection of MnSOD transcripts in proliferating normal and cancer cells.

    abstract::Manganese superoxide dismutase (MnSOD) is a nuclear encoded and mitochondrial matrix-localized redox enzyme that is known to regulate the cellular redox environment. Cellular redox environment changes during transitions between quiescent and proliferative cycles. Human MnSOD has two poly(A) sites resulting in two tran...


    pub_type: 杂志文章


    authors: Chaudhuri L,Nicholson AM,Kalen AL,Goswami PC

    更新日期:2012-03-08 00:00:00

  • Transforming growth factor-beta 1 inhibits cyclin D1 expression in intestinal epithelial cells.

    abstract::Transforming growth factor-beta 1 (TGF-beta 1) inhibits most epithelial cell types by blocking cell cycle progression during the G1 phase. D cyclins are normally expressed during G1 and are regulators of G1 progression. One of the crucial functions of D cyclins is their ability to bind to a cyclin-dependent kinase (Cd...


    pub_type: 杂志文章


    authors: Ko TC,Sheng HM,Reisman D,Thompson EA,Beauchamp RD

    更新日期:1995-01-05 00:00:00

  • Adenovirus-mediated transfer of wild-type p53 gene sensitizes TNF resistant MCF7 derivatives to the cytotoxic effect of this cytokine: relationship with c-myc and Rb.

    abstract::Tumor suppressor p53 is a nuclear transcription factor that blocks cell cycle progression and induces apoptosis. We have previously shown that the MCF7 resistance to the cytotoxic action of TNF correlates with p53 mutations. In the present study, we used a recombinant adenovirus carrying a wild-type p53 gene (Adwtp53)...


    pub_type: 杂志文章


    authors: Ameyar M,Shatrov V,Bouquet C,Capoulade C,Cai Z,Stancou R,Badie C,Haddada H,Chouaib S

    更新日期:1999-09-23 00:00:00

  • Post-transcriptional inactivation of p53 in immortalized murine embryo fibroblast cells.

    abstract::The steady-state levels of p53 mRNA and protein were barely detectable by Northern and Western blot analysis in spontaneously immortalized (10)3 and (10)7 murine embryo fibroblast (MEF) cells. But when cells were treated with cycloheximide (CHX) or emetine, expression levels were restored to those observed in primary ...


    pub_type: 杂志文章


    authors: Kim H,You S,Farris J,Foster LK,Foster DN

    更新日期:2001-05-31 00:00:00

  • Deletion of either C-terminal transactivation subdomain enhances the in vitro transforming activity of human transcription factor REL in chicken spleen cells.

    abstract::The REL gene is amplified in many human B-cell lymphomas and we have previously shown that expression of REL from a retroviral vector can malignantly transform chicken spleen cells in vitro. To identify REL protein functions necessary for malignant transformation, we have performed deletion analysis on REL sequences e...


    pub_type: 杂志文章


    authors: Starczynowski DT,Reynolds JG,Gilmore TD

    更新日期:2003-10-09 00:00:00

  • TAZ is required for metastatic activity and chemoresistance of breast cancer stem cells.

    abstract::Metastatic growth in breast cancer (BC) has been proposed as an exclusive property of cancer stem cells (CSCs). However, formal proof of their identity as cells of origin of recurrences at distant sites and the molecular events that may contribute to tumor cell dissemination and metastasis development are yet to be el...


    pub_type: 杂志文章


    authors: Bartucci M,Dattilo R,Moriconi C,Pagliuca A,Mottolese M,Federici G,Benedetto AD,Todaro M,Stassi G,Sperati F,Amabile MI,Pilozzi E,Patrizii M,Biffoni M,Maugeri-Saccà M,Piccolo S,De Maria R

    更新日期:2015-02-05 00:00:00

  • Calpain regulates sensitivity to trastuzumab and survival in HER2-positive breast cancer.

    abstract::Resistance to anti-HER2 (human epithelial growth factor receptor 2) trastuzumab therapy occurs commonly in HER2-positive breast cancer and involves overactivation of HER2 and/or AKT1. Using the model of trastuzumab-sensitive or trastuzumab-resistant HER2-positive cells with wild-type PTEN, negative regulator of AKT1, ...


    pub_type: 杂志文章


    authors: Kulkarni S,Reddy KB,Esteva FJ,Moore HC,Budd GT,Tubbs RR

    更新日期:2010-03-04 00:00:00

  • Retinoic acid receptor alpha suppresses polyomavirus transformation and c-fos expression in rat fibroblasts.

    abstract::To explore the molecular mechanisms by which retinoic acid inhibits oncogenic transformation, we have examined the effects of retinoic acid on the polyomavirus-induced transformation of rat fibroblasts. Treatment of rat F111 fibroblasts with high concentrations of retinoic acid (10(-6) M) partially inhibited the abili...


    pub_type: 杂志文章


    authors: Talmage DA,Lackey RS

    更新日期:1992-09-01 00:00:00

  • Promoter specificity and stability control of the p53-related protein p73.

    abstract::The p53 family of proteins play instrumental roles in mediating the cellular response to stress. The p53-related gene product, p73, occurs as two distinct protein isoforms, referred to as alpha and beta, which differ in the length of the C-terminal region and arise through alternative splicing of the p73 RNA. Here, we...


    pub_type: 杂志文章


    authors: Lee CW,La Thangue NB

    更新日期:1999-07-22 00:00:00

  • Loss of miR-125b-1 contributes to head and neck cancer development by dysregulating TACSTD2 and MAPK pathway.

    abstract::MicroRNAs (miRNAs) have important roles in the initiation and progression of human cancer, but their role in head and neck cancer development and progression is not well defined. We aimed to determine whether specific miRNAs and their target mRNAs contribute to head and neck cancer pathogenesis and progression. To ide...


    pub_type: 杂志文章


    authors: Nakanishi H,Taccioli C,Palatini J,Fernandez-Cymering C,Cui R,Kim T,Volinia S,Croce CM

    更新日期:2014-02-06 00:00:00

  • Genetic models of osteochondroma onset and neoplastic progression: evidence for mechanisms alternative to EXT genes inactivation.

    abstract::Osteochondroma, the most common benign bone tumor, may occur as a sporadic lesion or as multiple neoplasms in the context of multiple osteochondromas syndrome. The most severe complication is malignant transformation into peripheral secondary chondrosarcoma. Although both benign conditions have been linked to defects ...


    pub_type: 杂志文章


    authors: Zuntini M,Pedrini E,Parra A,Sgariglia F,Gentile FV,Pandolfi M,Alberghini M,Sangiorgi L

    更新日期:2010-07-01 00:00:00

  • Delta9-Tetrahydrocannabinol inhibits epithelial growth factor-induced lung cancer cell migration in vitro as well as its growth and metastasis in vivo.

    abstract::Delta(9)-Tetrahydrocannabinol (THC) is the primary cannabinoid of marijuana and has been shown to either potentiate or inhibit tumor growth, depending on the type of cancer and its pathogenesis. Little is known about the activity of cannabinoids like THC on epidermal growth factor receptor-overexpressing lung cancers,...


    pub_type: 杂志文章


    authors: Preet A,Ganju RK,Groopman JE

    更新日期:2008-01-10 00:00:00

  • Identification of AFAP1L1 as a prognostic marker for spindle cell sarcomas.

    abstract::Spindle cell sarcomas consist of tumors with different biological features, of which distant metastasis is the most ominous sign for a poor prognosis. However, metastasis is difficult to predict on the basis of current histopathological analyses. We have identified actin filament-associated protein 1-like 1 (AFAP1L1) ...


    pub_type: 杂志文章


    authors: Furu M,Kajita Y,Nagayama S,Ishibe T,Shima Y,Nishijo K,Uejima D,Takahashi R,Aoyama T,Nakayama T,Nakamura T,Nakashima Y,Ikegawa M,Imoto S,Katagiri T,Nakamura Y,Toguchida J

    更新日期:2011-09-22 00:00:00

  • Estrogen receptor beta growth-inhibitory effects are repressed through activation of MAPK and PI3K signalling in mammary epithelial and breast cancer cells.

    abstract::Two thirds of breast cancers express estrogen receptors (ER). ER alpha (ERα) mediates breast cancer cell proliferation, and expression of ERα is the standard choice to indicate adjuvant endocrine therapy. ERbeta (ERβ) inhibits growth in vitro; its effects in vivo have been incompletely investigated and its role in bre...


    pub_type: 杂志文章


    authors: Cotrim CZ,Fabris V,Doria ML,Lindberg K,Gustafsson JÅ,Amado F,Lanari C,Helguero LA

    更新日期:2013-05-09 00:00:00

  • Interaction between p53 and TGF beta 1 in control of epithelial cell proliferation.

    abstract::Although loss of sensitivity to transforming growth factor beta (TGF beta) may be a key step in the escape of epithelial tumours from normal growth control, the intracellular signals determining responsiveness remain controversial, particularly the role of p53. We have investigated this question using thyroid epitheli...


    pub_type: 杂志文章


    authors: Blaydes JP,Schlumberger M,Wynford-Thomas D,Wyllie FS

    更新日期:1995-01-19 00:00:00

  • The cell polarity regulator hScrib controls ERK activation through a KIM site-dependent interaction.

    abstract::The cell polarity regulator, human Scribble (hScrib), is a potential tumour suppressor whose loss is a frequent event in late-stage cancer development. Little is yet known about the mode of action of hScrib, although recent reports suggest its role in the regulation of cell signalling. In this study we show that hScri...


    pub_type: 杂志文章


    authors: Nagasaka K,Pim D,Massimi P,Thomas M,Tomaić V,Subbaiah VK,Kranjec C,Nakagawa S,Yano T,Taketani Y,Myers M,Banks L

    更新日期:2010-09-23 00:00:00

  • Praja1, a novel gene encoding a RING-H2 motif in mouse development.

    abstract::As part of a cloning strategy to identify genes involved in early mouse liver development we have isolated Praja1, a gene with similar sequences to the Drosophila melanogaster gene goliath (gl) which is involved in the fate of mesodermal cells ultimately forming gut musculatures, fat body, and the heart. Praja1 is a 2...


    pub_type: 杂志文章


    authors: Mishra L,Tully RE,Monga SP,Yu P,Cai T,Makalowski W,Mezey E,Pavan WJ,Mishra B

    更新日期:1997-11-06 00:00:00

  • In vitro reconstruction of tumour initiation in a human epithelium.

    abstract::Knowledge of tumour initiation in human epithelia is limited by sample availability and difficulty in experimental manipulation of human cells. The thyroid is a useful model since, in addition to multiple tumour stages, it presents two distinct 'pathways' of tumorigenesis: 'follicular' tumours, in which ras oncogene m...


    pub_type: 杂志文章


    authors: Bond JA,Wyllie FS,Rowson J,Radulescu A,Wynford-Thomas D

    更新日期:1994-01-01 00:00:00

  • Hsp90-inhibitor geldanamycin abrogates G2 arrest in p53-negative leukemia cell lines through the depletion of Chk1.

    abstract::Checkpoint protein Chk1 has been identified as an Hsp90 client. Treatment with 100 nM geldanamycin (GM) for 24 h markedly reduced the Chk1 amount in Jurkat and ML-1 leukemia cell lines. Because Chk1 plays a central role in G2 checkpoint, we added GM to G2-arrested Jurkat and HL-60 cells pretreated with 50 nM doxorubic...


    pub_type: 杂志文章


    authors: Sugimoto K,Sasaki M,Isobe Y,Tsutsui M,Suto H,Ando J,Tamayose K,Ando M,Oshimi K

    更新日期:2008-05-15 00:00:00

  • Silencing effect of CpG island hypermethylation and histone modifications on O6-methylguanine-DNA methyltransferase (MGMT) gene expression in human cancer.

    abstract::O6-methylguanine-DNA methyltransferase (MGMT) repairs the cytotoxic and mutagenic O6-alkylguanine produced by alkylating agents such as chemotherapeutic agents and mutagens. Recent studies have shown that in a subset of tumors, MGMT expression is inversely linked to hypermethylation of the CpG island in the promoter r...


    pub_type: 杂志文章


    authors: Nakagawachi T,Soejima H,Urano T,Zhao W,Higashimoto K,Satoh Y,Matsukura S,Kudo S,Kitajima Y,Harada H,Furukawa K,Matsuzaki H,Emi M,Nakabeppu Y,Miyazaki K,Sekiguchi M,Mukai T

    更新日期:2003-12-04 00:00:00

  • Transformation of Madin-Darby canine kidney (MDCK) epithelial cells by Epstein-Barr virus latent membrane protein 1 (LMP1) induces expression of Ets1 and invasive growth.

    abstract::The Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) has a significant role in initiating EBV-associated lymphoproliferative disease and EBV-related malignancies. In view of clinical features related to the type of EBV latency, LMP1 may influence invasiveness of EBV associated tumors categorized as ty...


    pub_type: 杂志文章


    authors: Kim KR,Yoshizaki T,Miyamori H,Hasegawa K,Horikawa T,Furukawa M,Harada S,Seiki M,Sato H

    更新日期:2000-03-30 00:00:00

  • Bloom's syndrome protein response to ultraviolet-C radiation and hydroxyurea-mediated DNA synthesis inhibition.

    abstract::Bloom's syndrome (BS) arises through mutations in both copies of the BLM gene that encodes a RecQ 3'-5' DNA helicase. BS patients are predisposed to developing all the cancers that affect the general population, and BS cells exhibit marked genetic instability. We showed recently that BLM protein contributes to the cel...


    pub_type: 杂志文章


    authors: Ababou M,Dumaire V,Lécluse Y,Amor-Guéret M

    更新日期:2002-03-27 00:00:00

  • Expression of the L-myc gene is under positive control by short-lived proteins.

    abstract::The c-myc oncogene is the most extensively studied member of the myc gene family which now consists of three characterized members, namely the c-myc, N-myc and L-myc genes. These genes are often found amplified in cell lines from small cell carcinomas of the lung (SCLC). In this study the L-myc gene was examined in a ...


    pub_type: 杂志文章


    authors: Saksela K

    更新日期:1987-01-01 00:00:00

  • Oxamflatin: a novel compound which reverses malignant phenotype to normal one via induction of JunD.

    abstract::In the course of screening for inhibitors of tumorigenic phenotype of K-ras-transformed NIH3T3 cells (DT cells), we found a novel compound, oxamflatin, an aromatic sulfonamide hydroxamate derivative, which induces flat phenotype in these cells and suppresses their anchorage-independent growth. In contrast to DT cells,...


    pub_type: 杂志文章


    authors: Sonoda H,Nishida K,Yoshioka T,Ohtani M,Sugita K

    更新日期:1996-07-04 00:00:00

  • Ras adenoviruses modulate cyclin E protein expression and DNA synthesis after partial hepatectomy.

    abstract::Ras-genes encode for proteins important for transmitting extracellular signals from the cytoplasm to the nucleus. In this study we investigated the impact of Ras on cell cycle progression after hepatectomy by using adenoviral vectors (adv) expressing beta-galactosidase (beta-gal), a dominant-negative (Ras N17) or a do...


    pub_type: 杂志文章


    authors: Lüdde T,Kubicka S,Plümpe J,Liedtke C,Manns MP,Trautwein C

    更新日期:2001-08-30 00:00:00

  • Kit signaling and negative regulation of daunorubicin-induced apoptosis: role of phospholipase Cgamma.

    abstract::Previous studies have demonstrated that activation of Kit by stem cell factor (SCF), its natural ligand, or by gain-of-function point mutation in its intracellular domain, confers significant protection against apoptosis induced by growth factor deprivation or radiation. However, the effects of Kit activation on the c...


    pub_type: 杂志文章


    authors: Plo I,Lautier D,Casteran N,Dubreuil P,Arock M,Laurent G

    更新日期:2001-10-11 00:00:00

  • EBP1 is a nucleolar growth-regulating protein that is part of pre-ribosomal ribonucleoprotein complexes.

    abstract::EBP1 was identified as a protein that interacts with the ErbB-3 receptor and possibly contributes to transducing growth regulatory signals. The existence of EBP1 homologs across species from simple eukaryotes to humans and its wide tissue expression pattern suggest that EBP1 acts as a general signaling molecule. We pr...


    pub_type: 杂志文章


    authors: Squatrito M,Mancino M,Donzelli M,Areces LB,Draetta GF

    更新日期:2004-05-27 00:00:00

  • A Herpes saimiri oncogene causing peripheral T-cell lymphoma in transgenic mice.

    abstract::Herpesvirus saimiri is an oncogenic virus causing rapid T-cell lymphomas in New World primates and rabbits. Deletion analysis of one strain of H saimiri has indicated an open reading frame, StpA, necessary for oncongenicity in monkeys. We have investigated the function of StpA in tumor induction by the generation of t...


    pub_type: 杂志文章


    authors: Kretschmer C,Murphy C,Biesinger B,Beckers J,Fickenscher H,Kirchner T,Fleckenstein B,Rüther U

    更新日期:1996-04-18 00:00:00

  • Proviral integrations at the Evi5 locus disrupt a novel 90 kDa protein with homology to the Tre2 oncogene and cell-cycle regulatory proteins.

    abstract::Evi5 is a common site of retroviral integration in T-cell lymphomas of AKXD mice. Mapping studies have localized Evi5 to a region approximately 18 kb upstream of another common viral integration site, Gfi1, on mouse chromosome 5 (Liao X, Jenkins NA and Copeland NG, (1995a). J. Virol., 69, 7132-7137). Gfi1 encodes a zi...


    pub_type: 杂志文章


    authors: Liao X,Du Y,Morse HC 3rd,Jenkins NA,Copeland NG

    更新日期:1997-03-06 00:00:00

  • All-trans retinoic acid treatment of Wilms tumor cells reverses expression of genes associated with high risk and relapse in vivo.

    abstract::Wilms tumor is one of the most frequent neoplasias in children. Our previous microarray screening in a large series of Wilms tumors revealed several candidate genes that are deregulated in advanced tumors and are part of the retinoic acid signaling pathway. To investigate whether retinoic acid could be employed as a n...


    pub_type: 杂志文章


    authors: Zirn B,Samans B,Spangenberg C,Graf N,Eilers M,Gessler M

    更新日期:2005-08-04 00:00:00