Evaluation of the antitumor effects of c-Myc-Max heterodimerization inhibitor 100258-F4 in ovarian cancer cells

• DOI: 10.1186/s12967-014-0226-x
• Publication Date: 2014-08-20T09:31:00Z
• Authors: Jiandong Wang; Xiaoli Ma; Hannah M Jones; Leo Li-Ying Chan; Fang Song; Weiyuan Zhang; Victoria L Bae-Jump; Chunxiao Zhou
• Keywords: Medicine(all); Ovarian Neoplasms; 0301 basic medicine; Biochemistry, Genetics and Molecular Biology(all); Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Research; Antineoplastic Agents; Apoptosis; Cell Cycle Checkpoints; Carcinoma, Ovarian Epithelial; 3. Good health; Proto-Oncogene Proteins c-myc; Thiazoles; 03 medical and health sciences; Tumor Cells, Cultured; Humans; Female; Molecular Targeted Therapy; Neoplasms, Glandular and Epithelial; Drug Screening Assays, Antitumor; Protein Multimerization; Tumor Stem Cell Assay; Cell Proliferation

Epithelial ovarian carcinoma is the most lethal gynecological cancer due to its silent onset and recurrence with resistance chemotherapy. Overexpression of oncogene c-Myc one frequently encountered events present in carcinoma. Disrupting function downstream target genes a promising strategy for therapy. Our objective was evaluate potential effects small-molecule inhibitor, 10058-F4, on cells underlying mechanisms by which 10058-F4 exerts actions. Using MTT assay, colony formation, flow cytometry Annexin V FITC assays, we found that significantly inhibited cell proliferation both SKOV3 Hey dose dependent manner through induction apoptosis cycle G1 arrest. Treatment reduced cellular ATP production ROS levels cells. Consistently, primary cultures treated showed caspase-3 activity inhibition 15 18 cases. The response independent level protein over-expression These novel findings suggest growth upon c-MYC targeting c-Myc-Max heterodimerization could be therapeutic cancer.