Regulation of Tumor Signaling Pathways by AZD3409 In Vitro

Background: The antineoplastic activity of AZD3409 was evaluated in relation to paclitaxel in human breast (MDA-MB-231, BT-474) and ovarian (A2780, A2780cp) cancer cell lines. Biomarkers of apoptosis, protein prenylation, survival, angiogenesis and cellular growth were determined. Materials and Meth...

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Published inAnticancer research Vol. 26; no. 6B; pp. 4185 - 4189
Main Authors STREEPER, Robert, CAMPOS, David, CARRIZALES, Gilbert, STEPHENS, Trevor C, IZBICKA, Elzbieta
Format Journal Article
LanguageEnglish
Published Attiki International Institute of Anticancer Research 01.11.2006
Subjects
Antineoplastic Agents - pharmacology
Apoptosis - drug effects
Biological and medical sciences
Blotting, Western
Dose-Response Relationship, Drug
Enzyme-Linked Immunosorbent Assay
Gynecology. Andrology. Obstetrics
In Situ Nick-End Labeling
Mammary gland diseases
Medical sciences
Signal Transduction - drug effects
Tumors
Enzyme
ovarian cancer
Transferases
Ovary cancer
Biological marker
Breast cancer
Malignant tumor
biomarker
Farnesyl-diphosphate farnesyltransferase
In vitro
Female genital diseases
Mammary gland diseases
Ovarian diseases
Angiogenesis
Cancerology
Signaling pathway
Cell death
Farnesyl transferase inhibitor
Inhibitor
Neovascularization
Apoptosis
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Summary:Background: The antineoplastic activity of AZD3409 was evaluated in relation to paclitaxel in human breast (MDA-MB-231, BT-474) and ovarian (A2780, A2780cp) cancer cell lines. Biomarkers of apoptosis, protein prenylation, survival, angiogenesis and cellular growth were determined. Materials and Methods: Cytotoxicity was evaluated by MTS assay, and apoptosis was evaluated by TUNEL. Biomarkers were measured by Western blots and ELISA. Results: The IC 50 concentrations of AZD3409 in MDA-MB-231, BT-474, A2780 and A2780cp were 19.16, 5.69, 3.19, and 8.86 μM, respectively. The corresponding apoptogenic EC 50 concentrations were 6.81, 4.15, 1.54 and 4.59 μM. Conclusion: Farnesylation of HDJ-2 was inhibited in all cell lines. Secretion of VEGF, bFGF and MMP-1 were inhibited in the breast lines but augmented in the ovarian lines. AZD3409 increased Akt activation in breast lines and decreased it in ovarian lines, without effect on MEK or ERK activation. AZD3409 cytotoxicity is mediated in part by inhibition of farnesylation.
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ISSN:0250-7005
1791-7530