Measuring Antitumor Effect of c-Myr-Max heterodimerization inhibitor 100258-F4 on Ovarian Cancer Cells using Cellometer Imaging Cytometry
Poster Apr 21, 2015
Leo L. Chan, Jiandong Wang, Xiaoli Ma, Hannah M. Jones, Fang Song, Weiyuan Zhang, Victoria L. Bae-Jump, Chunxiao Zhou
Epithelial ovarian carcinoma is the most lethal gynecological cancer due to its silent onset and recurrence with resistance to chemotherapy. Overexpression of oncogene c-Mycis one of the most frequently encountered events present in ovarian carcinoma. Disrupting the function of c-Mycand its downstream target genes is a promising strategy for cancer therapy. In this work, we aimed to evaluate the potential effects of small-molecule c-Mycinhibitor, 10058-F4, on ovarian cancer cells and the underlying mechanisms by which 10058-F4 exerts its actions. Using Cellometer image cytometry for cell cycle and Annexin V apoptosis assays, flow cytometry, MTT assay, and colony formation, 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. These novel findings suggest that targeting c-Myc-Max heterodimerizationcould be a potential therapeutic strategy for ovarian cancer.
The nuclear receptors pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are closely related transcription factors that regulate the expression of phase I (cytochrome P450s), phase II metabolizing enzymes and transporter genes in response to xenobiotics, including prescription drugs.READ MORE