1. Evaluation of the antitumor effects of c-Myc-Max heterodimerization inhibitor 100258-F4 in ovarian cancer cells
- Author
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Xiaoli Ma, Hannah M Jones, Fang-Fang Song, Leo Li-Ying Chan, Victoria L. Bae-Jump, Weiyuan Zhang, Chunxiao Zhou, and Jiandong Wang
- Subjects
endocrine system diseases ,Antineoplastic Agents ,Apoptosis ,Therapeutics ,Biology ,Carcinoma, Ovarian Epithelial ,General Biochemistry, Genetics and Molecular Biology ,Proto-Oncogene Proteins c-myc ,03 medical and health sciences ,0302 clinical medicine ,Ovarian cancer ,Ovarian carcinoma ,Carcinoma ,medicine ,Tumor Cells, Cultured ,Humans ,MTT assay ,Molecular Targeted Therapy ,Neoplasms, Glandular and Epithelial ,Primary cell culture ,Tumor Stem Cell Assay ,030304 developmental biology ,Cell Proliferation ,Medicine(all) ,Ovarian Neoplasms ,0303 health sciences ,Oncogene ,Biochemistry, Genetics and Molecular Biology(all) ,Cell growth ,Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ,Research ,General Medicine ,Cell Cycle Checkpoints ,Cell cycle ,medicine.disease ,Molecular biology ,3. Good health ,Thiazoles ,c-Myc ,10058-F4 ,030220 oncology & carcinogenesis ,Cancer research ,Female ,Drug Screening Assays, Antitumor ,Protein Multimerization - Abstract
Epithelial ovarian carcinoma is the most lethal gynecological cancer due to its silent onset and recurrence with resistance to chemotherapy. Overexpression of oncogene c-Myc is one of the most frequently encountered events present in ovarian carcinoma. Disrupting the function of c-Myc and its downstream target genes is a promising strategy for cancer therapy. Our objective was to evaluate the potential effects of small-molecule c-Myc inhibitor, 10058-F4, on ovarian carcinoma cells and the underlying mechanisms by which 10058-F4 exerts its actions. Using MTT assay, colony formation, flow cytometry and Annexin V FITC assays, we found that 10058-F4 significantly inhibited cell proliferation of both SKOV3 and Hey ovarian cancer cells in a dose dependent manner through induction of apoptosis and cell cycle G1 arrest. Treatment with 10058-F4 reduced cellular ATP production and ROS levels in SKOV3 and Hey cells. Consistently, primary cultures of ovarian cancer treated with 10058-F4 showed induction of caspase-3 activity and inhibition of cell proliferation in 15 of 18 cases. The response to 10058-F4 was independent the level of c-Myc protein over-expression in primary cultures of ovarian carcinoma. These novel findings suggest that the growth of ovarian cancer cells is dependent upon c-MYC activity and that targeting c-Myc-Max heterodimerization could be a potential therapeutic strategy for ovarian cancer.
- Published
- 2014