Triptolide sensitizes breast cancer cells to Doxorubicin through the DNA damage response inhibition.

Abstract:

:Triptolide is an active component from a Chinese herb, Tripterygium wilfordii which has been applied for treating immune-related diseases over centuries. Recently, it was reported that a variety of cancer cell lines could be sensitized to DNA-damage based chemotherapy drugs in combination with Triptolide treatment. In the present study, we show that a short time exposure (3 h) to Triptolide, which did not trigger apoptosis, could specifically increase breast cancer cells sensitivity to Doxorubicin rather than other chemotherapy drugs including Paclitaxel, Fluorouracil, and Mitomycin C. Further studies revealed Triptolide downregulated ATM expression and inhibited DNA damage response to DNA double- strand breaks. Moreover, the chemosensitization effect to Doxorubicin from Triptolide was attenuated by overexpression of ATM in breast cancer cells. Our findings suggest that Triptolide specifically chemosensitizes breast cancer cells to Doxorubicin prior to apoptosis initiation through downregulating ATM expression and inhibiting DNA damage response.

journal_name

Mol Carcinog

journal_title

Molecular carcinogenesis

authors

Deng Y,Li F,He P,Yang Y,Yang J,Zhang Y,Liu J,Tong Y,Li Q,Mei X,Shu Z,Zhao Q

doi

10.1002/mc.22795

subject

Has Abstract

pub_date

2018-06-01 00:00:00

pages

807-814

issue

6

eissn

0899-1987

issn

1098-2744

journal_volume

57

pub_type

杂志文章
  • Correlation of increased levels of Ha-ras T24 protein with extent of loss of gap junction function in rat liver epithelial cells.

    abstract::Although it is known that cells transformed by ras and other oncogenes show reduced gap junction function, to date there has been no investigation of the quantitative relationship between intracellular levels of ras oncoprotein and loss of cell-cell communication. Using the rat liver epithelial cell line MTR6, which c...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.2940050307

    authors: de Feijter AW,Trosko JE,Krizman DB,Lebovitz RM,Lieberman MW

    更新日期:1992-01-01 00:00:00

  • Prognostic implications of ezrin expression in human hepatocellular carcinoma.

    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

    authors: Kang YK,Hong SW,Lee H,Kim WH

    更新日期:2010-09-01 00:00:00

  • Induction of karyotype instability in a murine tumor cell line by quercetin, 2-amino-1-methyl-6 phenylimidazo[4,5-b]pyridine, and okadaic acid, as revealed by transmission distortion of the inactive X chromosome.

    abstract::Quercetin, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and okadaic acid are found in various foods and have been shown to have mutagenic or promoter-like activity. The effects of these three compounds on the transmission of the inactive X chromosome were examined in MST-C6 murine tumor cells, which were de...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.2940140411

    authors: Kuwabara K,Odani S,Takahashi Y,Arakawa M,Takagi N,Nagao M,Kominami R

    更新日期:1995-12-01 00:00:00

  • Loss of heterozygosity on chromosomes 1, 11, 12, and 14 in hybrid mouse lung adenocarcinomas.

    abstract::An allelotype analysis of lung tumors in mouse hybrids was conducted to identify common regions of allelic loss. By using 50 informative genetic markers, the autosomes of 36 (A/J x C3H/HeJ) F1 adenocarcinomas were examined. Additional adenocarcinomas from as many as 72 (C3H/HeJ x A/J) F1 and 15 (BALB/cJ x DBA/2J) F1 h...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/(SICI)1098-2744(199606)16:2<83::AID-MC4>3.

    authors: Herzog CR,Chen B,Wang Y,Schut HA,You M

    更新日期:1996-06-01 00:00:00

  • Regulation of keratinocyte growth factor expression in human endometrium: implications for hormonal carcinogenesis.

    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

    authors: Li Y,Rinehart CA

    更新日期:1998-12-01 00:00:00

  • Differential expression of p16(INK4a) in azoxymethane-induced mouse colon tumorigenesis.

    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;

    authors: Wang QS,Papanikolaou A,Nambiar PR,Rosenberg DW

    更新日期:2000-07-01 00:00:00

  • LncRNA DANCR promotes tumor growth and angiogenesis in ovarian cancer through direct targeting of miR-145.

    abstract::Differentiation antagonizing non-protein coding RNA (DANCR) is a newly identified oncogenic long noncoding RNA found in various cancers. However, the functional role of DANCR in tumor angiogenesis and the underlying mechanisms are still unclear. The expression of DANCR was determined in ovarian malignant tissues and c...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.23117

    authors: Lin X,Yang F,Qi X,Li Q,Wang D,Yi T,Yin R,Zhao X,Zhong X,Bian C

    更新日期:2019-12-01 00:00:00

  • Expression of peptidylarginine deiminase type 4 (PAD4) in various tumors.

    abstract::Peptidylarginine deiminase type 4 (PAD4/PADI4) posttranslationally converts peptidylarginine to citrulline, in a process known as citrullination. Evidence suggests that PAD4 plays an essential role in pathogenesis of rheumatoid arthritis (RA). RA synovium has many features in common with tumor tissues, including abnor...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20169

    authors: Chang X,Han J

    更新日期:2006-03-01 00:00:00

  • Molecular determinants of tumor differentiation in papillary serous ovarian carcinoma.

    abstract::In epithelial ovarian cancer, tumor grade is an independent prognosticator whose molecular determinants remain unknown. We investigated patterns of gene expression in well- and poorly differentiated serous papillary ovarian and peritoneal carcinomas with cDNA microarrays. A 6500-feature cDNA microarray was used for co...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.10098

    authors: Jazaeri AA,Lu K,Schmandt R,Harris CP,Rao PH,Sotiriou C,Chandramouli GV,Gershenson DM,Liu ET

    更新日期:2003-02-01 00:00:00

  • Possible involvement of c-myc but not ras genes in hepatocellular carcinomas developing after spontaneous hepatitis in LEC rats.

    abstract::LEC (Long-Evans with a cinnamon-like coat color) rats develop hepatocellular carcinomas (HCCs) spontaneously. We examined mutations of codons 12, 13, and 61 of the Ha-ras, Ki-ras, and N-ras genes in four HCCs by the polymerase chain reaction (PCR)-single-stranded DNA direct sequencing method. No ras gene mutations wer...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.2940040405

    authors: Fujimoto Y,Ishizaka Y,Tahira T,Sone H,Takahashi H,Enomoto K,Mori M,Sugimura T,Nagao M

    更新日期:1991-01-01 00:00:00

  • Dual use of hematopoietic and mesenchymal stem cells enhances engraftment and immune cell trafficking in an allogeneic humanized mouse model of head and neck cancer.

    abstract::In this report, we describe in detail the evolving procedures to optimize humanized mouse cohort generation, including optimal conditioning, choice of lineage for engraftment, threshold for successful engraftment, HNSCC tumor implantation, and immune and stroma cell analyses. We developed a dual infusion protocol of h...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22887

    authors: Morton JJ,Keysar SB,Perrenoud L,Chimed TS,Reisinger J,Jackson B,Le PN,Nieto C,Gomez K,Miller B,Gao D,Somerset H,Wang XJ,Jimeno A

    更新日期:2018-11-01 00:00:00

  • EGFR-mediated Akt and MAPKs signal pathways play a crucial role in patulin-induced cell proliferation in primary murine keratinocytes via modulation of Cyclin D1 and COX-2 expression.

    abstract::Patulin (PAT), a present day major contaminant of commercial apple and apple products is reported to be carcinogenic, embryotoxic, and immunotoxic. While oral and inhalation are considered to be the most prevalent routes of exposure to this toxin, exposure through skin is now being extensively investigated. Our previo...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22060

    authors: Alam S,Pal A,Kumar R,Dwivedi PD,Das M,Ansari KM

    更新日期:2014-12-01 00:00:00

  • Distinct roles of individual Smads in skin carcinogenesis.

    abstract::Transforming growth factor beta (TGFbeta) signaling has both tumor suppression and promotion roles. Smads are transcription factors that primarily mediate intracellular signaling for the TGFbeta superfamily. Loss of Smad2 and Smad4, but not Smad3 is common in human cancers. Given the complex nature of TGFbeta signalin...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章,评审

    doi:10.1002/mc.20336

    authors: Bornstein S,Hoot K,Han GW,Lu SL,Wang XJ

    更新日期:2007-08-01 00:00:00

  • Lasp2 enhances tumor invasion via facilitating phosphorylation of FAK and predicts poor overall survival of non-small cell lung cancer patients.

    abstract::Lasp2, as well as Lasp1, is a member of the LIM-protein subfamily of the nebulin group characterized by the combined presence of LIM and SH3 domains. Lasp1 and Lasp2 are highly conserved in their LIM, nebulin-like, and SH3 domains but differ significantly at their linker regions. Lasp1 had been described as an oncogen...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22700

    authors: Zhang X,Cai L,Zhou H,Liu Y,Fan C,Wang L,Li A,Miao Y,Li Q,Qiu X,Wang E

    更新日期:2017-12-01 00:00:00

  • The tumor suppressor parafibromin is required for posttranscriptional processing of histone mRNA.

    abstract::Parafibromin, encoded by the gene HRPT2, is a tumor suppressor protein associated with the RNA polymerase II-associated complex, Paf1 complex. HRPT2 mutations were first identified in patients with the multiple endocrine neoplasia syndrome, hyperparathyroidism-jaw tumor (HPT-JT) syndrome, and have also been found in s...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20591

    authors: Farber LJ,Kort EJ,Wang P,Chen J,Teh BT

    更新日期:2010-03-01 00:00:00

  • Microarray meta-analysis defines global angiogenesis-related gene expression signatures in human carcinomas.

    abstract::Angiogenesis is a prerequisite for progression of cancers. The number of genes linked to angiogenesis suggests the existence of complex gene-networks, which remain to be elucidated. To identify angiogenesis genes deregulated in carcinomas, we performed a meta-profiling analysis of published gene expression microarray ...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章,meta分析

    doi:10.1002/mc.20874

    authors: Anders M,Fehlker M,Wang Q,Wissmann C,Pilarsky C,Kemmner W,Höcker M

    更新日期:2013-01-01 00:00:00

  • Lidamycin inhibits tumor initiating cells of hepatocellular carcinoma Huh7 through GSK3β/β-catenin pathway.

    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

    authors: Chen Y,Yu D,Zhang C,Shang B,He H,Chen J,Zhang H,Zhao W,Wang Z,Xu X,Zhen Y,Shao RG

    更新日期:2015-01-01 00:00:00

  • Mitochondrial bioenergetic background confers a survival advantage to HepG2 cells in response to chemotherapy.

    abstract::Cancer cells mainly rely on glycolysis for energetic needs, and mitochondrial ATP production is almost inactive. However, cancer cells require the integrity of mitochondrial functions for their survival, such as the maintenance of the internal membrane potential gradient (DeltaPsim). It thus may be predicted that Delt...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20539

    authors: Loiseau D,Morvan D,Chevrollier A,Demidem A,Douay O,Reynier P,Stepien G

    更新日期:2009-08-01 00:00:00

  • Gradual deregulation and loss of PCPH expression in the progression of human laryngeal neoplasia.

    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

    authors: Blánquez MJ,Regadera J,Mariño J,Newman RE,Notario V

    更新日期:2002-12-01 00:00:00

  • Expression and localization of the matrix metalloproteinase pump-1 (MMP-7) in human gastric and colon carcinomas.

    abstract::The expression of members of the family of matrix-degrading metalloproteinases (MMPs) is believed to contribute to the complex process of invasion and metastasis. In this study, specific cDNA probes for three members of the stromelysin subfamily of MMPs--stromelysin (MMP-3), stromelysin-2 (MMP-10), and pump-1 (MMP-7)-...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.2940040617

    authors: McDonnell S,Navre M,Coffey RJ Jr,Matrisian LM

    更新日期:1991-01-01 00:00:00

  • Decreased expression of the growth hormone receptor and growth hormone binding protein in rat liver nodules.

    abstract::The growth hormone receptor (GHR) and growth hormone-binding protein (GH-BP) expression were characterized in liver nodules and hepatomas from male Wistar rats. The mRNA levels of GHR and GH-BP, studied by northern blot analysis and solution hybridization, were 35-50% (in nodules) and 2-6% (in hepatomas) of the level ...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.2940030309

    authors: Levinovitz A,Husman B,Eriksson LC,Norstedt G,Andersson G

    更新日期:1990-01-01 00:00:00

  • Potentially functional polymorphisms in DNA repair genes and non-small-cell lung cancer survival: a pathway-based analysis.

    abstract::To assess systematically whether potentially functional polymorphisms in DNA repair genes influence the clinical behavior of non-small-cell lung cancer (NSCLC), we examined the impact of a comprehensive panel of 218 signal nucleotide polymorphisms (SNP) in 50 candidate DNA repair genes on overall survival of NSCLC in ...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20819

    authors: Dong J,Hu Z,Shu Y,Pan S,Chen W,Wang Y,Hu L,Jiang Y,Dai J,Ma H,Jin G,Shen H

    更新日期:2012-07-01 00:00:00

  • ETS1 is coexpressed with ZEB2 and mediates ZEB2-induced epithelial-mesenchymal transition in human tumors.

    abstract::Epithelial-mesenchymal transition (EMT) is an embryonic program that is reactivated in cancer and regulates the invasion and metastasis of tumor cells. Zinc finger E-box binding homeobox 2 (ZEB2) induces EMT by upregulating matrix metalloproteinases (MMP), yet MMP genes lack ZEB2 binding motif in their promoters. Rece...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22994

    authors: Yalim-Camci I,Balcik-Ercin P,Cetin M,Odabas G,Tokay N,Sayan AE,Yagci T

    更新日期:2019-06-01 00:00:00

  • A p53 mutation in exon 5 associated with adenovirus transformation.

    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

    authors: Eyler YL,Siwarski DF,Huppi KE,Lewis AM Jr

    更新日期:1995-01-01 00:00:00

  • Long non-coding RNA-LET is a positive prognostic factor and exhibits tumor-suppressive activity in gallbladder cancer.

    abstract::The identification of cancer-associated long non-coding RNAs (lncRNAs) and the investigation of their molecular and biological functions are vital for understanding the molecular biology and progression of cancer. The lncRNA-LET, a newly identified lncRNA, was demonstrated to be down-regulated in hepatocellular cancer...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22215

    authors: Ma MZ,Kong X,Weng MZ,Zhang MD,Qin YY,Gong W,Zhang WJ,Quan ZW

    更新日期:2015-11-01 00:00:00

  • Midkine in the progression of rat N-nitroso-N-methylurea-induced mammary tumors.

    abstract::Recent studies have implicated a role for midkine (MK) in cancer progression. This is based upon its structural homology with pleiotrophin, an angiogenic growth factor, and its ability to enhance fibrinolytic activity of bovine endothelial cells. To investigate whether MK plays a role in breast cancer, we examined MK ...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/(SICI)1098-2744(199611)17:3<112::AID-MC2>3

    authors: Chen Y,McKenzie KE,Aldaz CM,Sukumar S

    更新日期:1996-11-01 00:00:00

  • Kaempferol suppresses bladder cancer tumor growth by inhibiting cell proliferation and inducing apoptosis.

    abstract::The effects of the flavonoid compound, kaempferol, which is an inhibitor of cancer cell proliferation and an inducer of cell apoptosis have been shown in various cancers, including lung, pancreatic, and ovarian, but its effect has never been studied in bladder cancer. Here, we investigated the effects of kaempferol on...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22154

    authors: Dang Q,Song W,Xu D,Ma Y,Li F,Zeng J,Zhu G,Wang X,Chang LS,He D,Li L

    更新日期:2015-09-01 00:00:00

  • Aberrant transforming growth factor-beta signaling in azoxymethane-induced mouse colon tumors.

    abstract::Alterations in the transforming growth factor-beta (TGF-beta) pathway are implicated in the pathogenesis of colorectal cancer. We hypothesize that alterations in the TGF-beta pathway contribute to differential sensitivity of mice to the colon carcinogen azoxymethane (AOM). A/J (sensitive) and AKR/J (resistant) mice we...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.1055

    authors: Guda K,Giardina C,Nambiar P,Cui H,Rosenberg DW

    更新日期:2001-08-01 00:00:00

  • Antitumor effects of circ-EPHB4 in hepatocellular carcinoma via inhibition of HIF-1α.

    abstract::The protein EPHB4 plays a vital role in various tumor types. However, few studies into the function of circ-EPHB4 (hsa_circ_0001730) in tumors have been conducted. This study aimed to investigate the functions of circ-EPHB4 and the underlying mechanism of circ-EPHB4 in regulating hepatocellular carcinoma (HCC). The ex...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22976

    authors: Tan Y,Du B,Zhan Y,Wang K,Wang X,Chen B,Wei X,Xiao J

    更新日期:2019-06-01 00:00:00

  • Effects of supplemental calcium and vitamin D on tight-junction proteins and mucin-12 expression in the normal rectal mucosa of colorectal adenoma patients.

    abstract::The physical gut barrier, comprised of a thick mucus layer and the epithelium, plays an important role in defense against microbes and foreign antigens. Calcium and vitamin D may be involved in maintaining the integrity of the intestinal mucosal barrier, the dysfunction of which may lead to endotoxemia and inflammatio...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1002/mc.23010

    authors: Mandle HB,Jahan FA,Bostick RM,Baron JA,Barry EL,Yacoub R,Merrill J,Rutherford RE,Seabrook ME,Fedirko V

    更新日期:2019-07-01 00:00:00