Effect of cisplatin and c-myb antisense phosphorothioate oligodeoxynucleotides combination on a human colon carcinoma cell line in vitro and in vivo

Bufalo, Donatella Del; Cucco, Carla; Leonetti, Carlo; Citro, Gennaro; D’Agnano, Igea; Benassi, Maria Serena; Geiser, Timothy; Zon, Gerald; Calabretta, Bruno; Zupi, Gabriella

doi:10.1038/bjc.1996.370

Cited by 21 publications

(8 citation statements)

References 27 publications

(18 reference statements)

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“…Cisplatin exerts its antiproliferative activity independently of a direct effect on c-myb expression, as c-myb mRNA levels were not downregulated in cultures treated with cisplatin alone. The in vitro results were validated by the in vivo data showing a significant increase of tumor mass inhibition following the combination treatment without toxic effects (Del Bufalo et al, 1996). The ability of c-myb PS ASOs to sensitize human colon cancer cells to cisplatin was confirmed by a study performed by Funato et al (2001).…”

Section: C-mybsupporting

confidence: 51%

The future of antisense therapy: combination with anticancer treatments

Biroccio¹,

Leonetti²,

Zupi³

2003

Oncogene

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Section: C-mybsupporting

confidence: 51%

The future of antisense therapy: combination with anticancer treatments

Biroccio¹,

Leonetti²,

Zupi³

2003

Oncogene

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“…These data agree with those of other investigators confirming the antiproliferative effect of c-myb antisense ODNs and its potential usefulness for the systemic treatment of solid and nonsolid tumors [42,43]. In particular, our results are consistent with those reported by Del Bufalo et al [44], whereas c-myb expression played an important role in LoVo Dx cell proliferation both in vitro and in vivo. Our results agree with those obtained by Hijiya et al [42], which suggest that the low levels of cmyb expression in the melanoma cell lines were biologically relevant as they were able to inhibit growth in vitro of two cell lines in a dose-responsive manner with antisense c-myb sequences.…”

Section: Discussionsupporting

confidence: 83%

Antisense Oligodeoxynucleotide Directed against c-myb Has Anticancer Activity and Potentiates the Antiproliferative Effect of Conventional Anticancer Drugs Acting by Different Mechanisms in Human Colorectal Cancer Cells

Abaza¹,

Al‐Attiyah²,

Al-Saffar³

et al. 2003

Tumor Biol

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The c-myb proto-oncogene encodes a DNA-binding protein with transactivation properties that plays an important regulatory role in cell proliferation and differentiation. Overexpression of c-myb in colonic tumors compared to normal mucosa suggests that c-myb may play a role in the malignant transformation of colonic mucosa and that inhibition of c-myb expression may suppress, to some extent, the proliferation of neoplastic cells. Complete suppression of tumor cell proliferation may require inhibition of multiple growth-promoting genes. Alternatively, the combination of oncogene-targeted oligodeoxynucleotides (ODNs) with standard cytotoxic agents might represent a useful therapeutic approach to improving cancer treatment. In the present study, we have investigated whether the inhibition of a growth-promoting gene, namely c-myb, affects the sensitivity of human colorectal cancer cells, in vitro, to conventional chemotherapeutic drugs: taxol, 5-fluorouracil, vinblastine and doxorubicin. We show that c-myb antisense phosphorothioate (S) ODN treatment induces growth arrest in the G₁/G₂ phases of the cell cycle and inhibits cell proliferation in a dose- and time-dependent manner. Also, treatment with c-myb antisense (S)ODN decreases c-myb mRNA and protein expression. A greater inhibition of cell proliferation in vitro was obtained with the combination of c-myb (S)ODN and cytotoxic drugs. The combinations exerted additive and synergistic effects on human colorectal cancer cells. This study suggests that c-myb antisense (S)ODN might be useful in the therapy of colorectal cancer in combination with chemotherapeutic drugs.

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“…39 LMB was kindly provided by Barbara Wolff, Novartis and was used at 10 nM for 18 h. Protease inhibitors were used for 16 h at the following concentrations: 10 mM lactacystin proteasome inhibitor (Biomol), 2 mM phenylmethylsulfonyl fluoride (PMSF) serine-protease inhibitor, 100 mM chloroquine lysosome inhibitor (Sigma), 40 or 100 mM Z-Val-Ala-DL-Aspfluoromethylketone (z-VAD-fmk) pan-caspase inhibitor, 6 or 60 mM ZAsp(OMe)-Glu(OMe)-Val-Asp(OMe)-fluoromethylketone (DEVD-fmk) caspase-3 inhibitor (also inhibits caspase-6, -7, -8, and -10), 100 mM Z-PheAla-fluoromethylketone (z-FA-fmk) negative control for caspase inhibitors (all from Calbiochem). MetOH and DMSO solvents were used as control.…”

Section: Methodsmentioning

confidence: 99%

p53 can inhibit cell proliferation through caspase-mediated cleavage of ERK2/MAPK

Marchetti

Cecchinelli²,

D'Angelo³

et al. 2004

Cell Death Differ

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Stimulation of the Ras/MAPK cascade can either activate p53 and promote replicative senescence and apoptosis, or degrade p53 and promote cell survival. Here we show that p53 can directly counteract the Ras/MAPK signaling by inactivating ERK2/MAPK. This inactivation is due to a caspase cleavage of the ERK2 protein and contributes to p53-mediated growth arrest. We found that in Ras-transformed cells, growth arrest induced by p53, but not p21 Waf1 , is associated with a strong reduction in ERK2 activity, phosphorylation, and protein half-life, and with the appearance of caspase activity. Likewise, DNA damage-induced cell cycle arrest correlates with p53-dependent ERK2 downregulation and caspase activation. Furthermore, caspase inhibitors or expression of a caspase-resistant ERK2 mutant interfere with ERK2 cleavage and restore proliferation in the presence of p53 activation, indicating that caspase-mediated ERK2 degradation contributes to p53-induced growth arrest. These findings strongly point to ERK2 as a novel p53 target in growth suppression.

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Effect of cisplatin and c-myb antisense phosphorothioate oligodeoxynucleotides combination on a human colon carcinoma cell line in vitro and in vivo

Cited by 21 publications

References 27 publications

The future of antisense therapy: combination with anticancer treatments

The future of antisense therapy: combination with anticancer treatments

Antisense Oligodeoxynucleotide Directed against c-myb Has Anticancer Activity and Potentiates the Antiproliferative Effect of Conventional Anticancer Drugs Acting by Different Mechanisms in Human Colorectal Cancer Cells

p53 can inhibit cell proliferation through caspase-mediated cleavage of ERK2/MAPK

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