5, 7-Dihalo-8-quinolinol complex inhibits growth of ovarian cancer cells via the downregulation of expression of Wip1

Han Qi,Rao Zhiwei,Xia Songbai

doi:10.4314/tjpr.v19i7.12

Abstract

Purpose: To assess the cytotoxic effect of 5, 7-dihalo-8-quinolinol complex (DHQ) on ovarian cancer cells, and the mechanism of action involved.Methods: DHQ-mediated changes in cell viability were determined using MTT assay, while apoptosis was analyzed with flow cytometry. The effect of DHQ on cell migration was determined using inverted microscopy, while its effect on invasiveness was assessed with Giemsa dyeing. FACS Caliburinstrumentation was employed for analyzing the effect of DHQ on the cell cycle. The protein expressions of Wip1 and P53 were assayed by western blotting.Results: DHQ induced cytotoxicity against A2780 and OVCAR 3 cells in the concentration range of 0.25 - 12 μM (p < 0.05). In A2780 and OVCAR 3 cells, treatment with 12 μMDHQ resulted in 69.34 and 65.46 % apoptosis, respectively. The migratory potential and invasiveness of A2780 and OVCAR3 cells were significantly decreased by 12 μMDHQ, relative to untreated cells (p < 0.05). Moreover, treatment with 12 μMDHQ arrested cell cycle at G1/G0 phase in A2780 and OVCAR3 cells, but downregulated the protein expressions of Wip1 expression in A2780 and OVCAR3 cells.Conclusion: DHQ exerts cytotoxic effect on ovarian cancer cell growth via arrest of cell cycle and activation of apoptosis. Moreover, DHQ inhibits the migratory and invasive abilities of the cells. Thus, DHQ is a potential drug candidate for the management of ovarian cancer. Keywords: 5,7-Dihalo-8-quinolinol complex, Ovarian cancer, Cytotoxicity, Apoptosis, Invasiveness, Migration, Cell cycle

Highlights

Ovarian carcinoma is one of the most lethal malignancies and the 5th highest cause of cancer-related deaths in the United States [1]
The high mortality of ovarian cancer is associated with resistance to chemotherapy, tumor recurrence and elevated metastatic potential [2]
The cytotoxic effects of dihalo-8-quinolinol complex (DHQ) on A2780 and OVCAR 3 cells were measured at different durations using MTT assay

Summary

INTRODUCTION

Ovarian carcinoma is one of the most lethal malignancies and the 5th highest cause of cancer-related deaths in the United States [1]. Slowly-growing ovarian cancers detected at initial stage are known as type I tumors [4]. Most ovarian cancer cells escape chemotherapeutic drugs by remaining in the non-proliferating and dormant stage [6] These dormant cancerous cells start proliferating when the effect of the chemotherapeutic agent subsides, leading to tumor relapse and failure of therapeutic strategy [6]. The anti-cancer effect of DHQ on ovarian cancer cells was investigated. The cells were treated with 12 μM DHQ or normal saline for 48 h, followed by washing with PBS at 37 ̊C. The cells were seeded at a density of 2 x 106 cells/well in 60-mm plates, and were treated with 12 μM DHQ or normal saline at 37 ̊C for 48 h. Thereafter, the distribution of cellular DNA content was determined using FACSCalibur instrumentation (BD Biosciences, San Jose, CA, USA)

RESULTS

DISCUSSION

CONCLUSION

Conflict of interest