Genotoxic Profiling of MCF-7 Breast Cancer Cell Line Elucidates Gene Expression Modifications Underlying Toxicity of the Anticancer Drug 2-(4-Amino-3-methylphenyl)-5-fluorobenzothiazole

Monks, Anne; Harris, Erik; Hose, Curtis; Connelly, John W.; Sausville, Edward A.

doi:10.1124/mol.63.3.766

Cited by 49 publications

(29 citation statements)

References 23 publications

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“…Of note, PDF has been shown to be induced in human colon cancer cells by several nonsteroidal anti-inflammatory drugs (33), as well as antitumorigenic compounds such as reveratrol (34), genistein (35), diallyl disulfide (36), and 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (5F-203; ref. 37), suggesting that PDF expression may be an important regulator of drug response. In contrast to our own data, the majority of previous studies suggest a proapoptotic role for PDF, with overexpression resulting in increased levels of spontaneous apoptosis in HCT116 colorectal (38) and DU-145 prostate cell lines (39) and enhanced indomethacin-induced apoptosis in HCT116 cells (33).…”

Section: Discussionmentioning

confidence: 99%

Pharmacogenomic Identification of Novel Determinants of Response to Chemotherapy in Colon Cancer

et al. 2006

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DNA microarray analysis was used to analyze the transcriptional profile of HCT116 colorectal cancer cells that were treated with 5-fluorouracil (5-FU) or oxaliplatin and selected for resistance to these agents. Bioinformatic analyses identified sets of genes that were constitutively dysregulated in drug-resistant cells and transiently altered following acute exposure of parental cells to drug. We propose that these genes may represent molecular signatures of sensitivity to 5-FU and oxaliplatin. Using real-time reverse transcription-PCR (RT-PCR), the robustness of our microarray data was shown with a strong overall concordance of expression trends for z82% (oxaliplatin) and z85% (5-FU) of a representative subset of genes. Furthermore, strong correlations between the microarray and real-time RT-PCR measurements of average fold changes in gene expression were observed for both the 5-FU (R 2 z 0.73) and oxaliplatin gene sets (R 2 z 0.63). Functional analysis of three genes identified in the microarray study [prostate-derived factor (PDF), calretinin, and spermidine/spermine N 1 -acetyl transferase (SSAT)] revealed their importance as novel regulators of cytotoxic drug response. These data show the power of this novel microarray-based approach to identify genes which may be important markers of response to treatment and/or targets for therapeutic intervention. (Cancer Res 2006; 66(5): 2765-77)

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Section: Discussionmentioning

confidence: 99%

Pharmacogenomic Identification of Novel Determinants of Response to Chemotherapy in Colon Cancer

et al. 2006

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“…36 CYP1A1 activation led to cytotoxicity of an anticancer agent through DNA damage-induced apoptosis toxicity. 37 CLU, also known as apolipoprotein J, has been implicated in numerous processes, including active cell death, its expression and apoptosis being localized in the same cells in pancreatic cancer.…”

Section: Discussionmentioning

confidence: 99%

Potential anticancer activity of tanshinone IIA against human breast cancer

et al. 2005

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Tanshinone IIA is a derivative of phenanthrene-quinone isolated from Danshen, a widely used Chinese herbal medicine. It has antioxidant properties and cytotoxic activity against multiple human cancer cell lines, inducing apoptosis and differentiation of some human cancer cell lines. Our purpose was to confirm its anticancer activity on human breast cancer in vitro and in vivo and to elucidate the mechanism of its activity. Human breast cancer cells were tested in vitro for cytotoxicity, colony formation inhibition, BrdU incorporation and gene expression profiling after treatment with tanshinone IIA. Seven nude mice bearing human breast infiltrating duct carcinoma orthotopically were tested for anticancer activity and expression of caspase-3 in vivo by s.c. injection of tanshinone IIA at a dose of 30 mg/kg 3 times/week for 10 weeks. Tanshinone IIA demonstrated a dose-and time-dependent inhibitory effect on cell growth (IC 50 = 0.25 mg/ml), and it significantly inhibited colony formation and BrdU incorporation of human breast cancer cells. Oligonucleotide microarray analysis identified 41 upregulated (1.22%) and 24 downregulated (0.71%) genes after tanshinone IIA treatment. Upregulated genes were involved predominantly in cycle regulation, cell proliferation, apoptosis, signal transduction and transcriptional regulation; and downregulated genes were associated mainly with apoptosis and extracellular matrix/adhesion molecules. A 44.91% tumor mass volume reduction and significant increase of casepase-3 protein expression were observed in vivo. Our findings suggest that tanshinone IIA might have potential anticancer activity on both ER-positive and -negative breast cancers, which could be attributed in part to its inhibition of proliferation and apoptosis induction of cancer cells through upregulation and downregulation of multiple genes involved in cell cycle regulation, cell proliferation, apoptosis, signal transduction, transcriptional regulation, angiogenesis, invasive potential and metastatic potential of cancer cells. ADPRTL1 might be the main target at which tanshinone IIA acted. ' 2005 Wiley-Liss, Inc.Key words: tanshinone IIA; anticancer activity; breast cancer; growth inhibition; apoptosis Breast cancer is a major public health problem in the United States and in most industrialized countries.1 It is the most common cancer in women and the leading cause of cancer death among women 35-54 years of age.2 The rising incidence and poor prognosis of breast cancer cases have prompted a search for additional preventive and therapeutic modalities.Danshen (Salvia miltiorrhiza Bunge) is a widely used Chinese herbal medicine; its extracts contain diterpene quinone and phenolic acid derivatives, including tanshinone (I, IIA and IIB), cryptotanshinone, isocryptotanshinone, miltirone, tanshinol (I and II) and salviol. These compounds have antioxidant properties and protect against lipid peroxidation in vitro and in vivo, making them potential antidotes for free radical-based disorders.3-5 Tanshinone IIA is a derivative of...

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“…However, NAG-1 has been shown to possess antitumorigenic and proapoptotic activity in some types of cancer cells (19,22,23). NAG-1 is up-regulated in several epithelial cancer cell lines by several nonsteroidal anti-inflammatory drugs (23), as well as by antitumorigenic compounds such as resveratrol (24), catechins (25), indole-3 carbinol (26), conjugated linoleic acid (27), PPARg ligands (13), DIM derivatives (28), horehound extracts (29), and 5F-203 (30). In contrast to other transforming growth factor-h superfamily genes, NAG-1 contains a p53 binding site in the 5 ¶ upstream region (19,22,23), and several dietary compounds induce NAG-1 expression via p53 (24,25).…”

Section: Introductionmentioning

confidence: 99%

A novel peroxisome proliferator–activated receptor γ ligand, MCC-555, induces apoptosis via posttranscriptional regulation of NAG-1 in colorectal cancer cells

Yamaguchi

Lee

Eling

et al. 2006

Molecular Cancer Therapeutics

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Apoptosis and/or differentiation induction caused by the peroxisome proliferator -activated receptor ; (PPAR;) ligand is a promising approach to cancer therapy. The thiazolidinedione derivative MCC-555 has an apoptotic activity in human colorectal cancer cells, accompanied by up-regulation of a proapoptotic nonsteroidal antiinflammatory drug -activated gene (NAG-1) in a PPAR;-independent manner. Treatment with MCC-555 resulted in the induction of NAG-1 expression and apoptosis in HCT-116 cells. Down-regulation of NAG-1 by small interfering RNA suppressed MCC-555-induced apoptosis. MCC-555 was found to affect NAG-1 mRNA stability. To further define the underlying mechanism of RNA stability affected by MCC-555, we cloned the 3 ¶-untranslated region (3 ¶UTR) of human NAG-1 mRNA, which contains four copies of an AU-rich element (ARE), downstream from the luciferase gene. The reporter activity was reduced to f70% by inserting the 3 ¶UTR. In addition, deletion of ARE sequences in the 3 ¶UTR or MCC-555 treatment substantially restored activity. This effect of MCC-555 on the ARE-mediated mRNA degradation was inhibited by extracellular signal -regulated kinase (ERK) pathway inhibitors. Subsequently, rapid phosphorylation of ERK1/2 by MCC-555 treatment was detected. Moreover, ERK small interfering RNA suppressed MCC-555-induced NAG-1 expression. These results suggest that ARE sequences in the 3 ¶UTR of the NAG-1 gene contribute to mRNA degradation and ERK1/2 phosphorylation is responsible for the stabilization of NAG-1 mRNA. These findings may provide a novel explanation for the antitumorigenic and/or proapoptotic action of MCC-555 in human colorectal cancer and the ability of pharmacologic approaches to be used against diseases caused by alterations of RNA stability. [Mol Cancer Ther 2006;5(5):1352 -61]

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Genotoxic Profiling of MCF-7 Breast Cancer Cell Line Elucidates Gene Expression Modifications Underlying Toxicity of the Anticancer Drug 2-(4-Amino-3-methylphenyl)-5-fluorobenzothiazole

Cited by 49 publications

References 23 publications

Pharmacogenomic Identification of Novel Determinants of Response to Chemotherapy in Colon Cancer

Pharmacogenomic Identification of Novel Determinants of Response to Chemotherapy in Colon Cancer

Potential anticancer activity of tanshinone IIA against human breast cancer

A novel peroxisome proliferator–activated receptor γ ligand, MCC-555, induces apoptosis via posttranscriptional regulation of NAG-1 in colorectal cancer cells

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