title: Evaluation of the antitumor effects of c-Myc-Max heterodimerization inhibitor 100258-F4 in ovarian cancer cells.
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.
authors.forename: Jiandong
authors.initials: J
authors.lastname: Wang
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Ma
authors.forename: Hannah M
authors.initials: HM
authors.lastname: Jones
authors.forename: Leo Li-Ying
authors.initials: LL
authors.lastname: Chan
authors.forename: Fang
authors.initials: F
authors.lastname: Song
authors.affiliation: Department of Gynecological Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China. zhangwy9921@hotmail.com.
authors.forename: Weiyuan
authors.initials: W
authors.lastname: Zhang
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Bae-Jump
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Zhou
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000077216:Carcinoma, Ovarian Epithelial; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D058990:Molecular Targeted Therapy; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D055503:Protein Multimerization / Q000187:drug effects; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013844:Thiazoles / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
chemical_list: C524814:5-(4-ethylbenzylidene)-2-thioxothiazolidin-4-one; D000970:Antineoplastic Agents; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C499330:MAX protein, human; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D013844:Thiazoles