Synergistic Effects of Nobiletin and Sorafenib Combination on Metastatic Prostate Cancer Cells

Abstract

Objective: Herein we, for the first time, investigated a potential synergistic effect of nobiletin (NOB) and sorafenib (SOR) on PC-3 prostate cancer and HUVEC control cell lines.

Methods: In order to determine the cytotoxic and apoptotic effects of the combination of NOB and SOR, WST-1, Annexin V, and cell cycle analysis were performed. The potential molecular mechanism of apoptotic cell death was assessed by Bax, Bcl-2, CCDN1, Rb1, and CDKN1A gene expression and acridine orange (AO) and DAPI staining.

Results: Our results indicated that NOB and SOR combination had a significant inhibitory effect on the viability of PC-3 cells with less toxicity on HUVEC cells than SOR alone (P < 0.01). NOB and SOR combination significantly caused much more apoptotic cell death and cell cycle arrest at G0/G1 phase by up-regulation of Bax, Rb1, and CDKN1A levels in PC-3 cells (P < 0.01). Therefore, strong synergistic effects between NOB and SOR were analyzed (CI < 1).

Conclusion: NOB and SOR combination was more effective than SOR and NOB alone and reduced the exposure time for SOR and NOB in PC-3 cells. Combination strategy is a therapeutic potential to improve efficacy and reduce side-effect of SOR for the treatment of metastatic prostate cancer cells.

Author’s Contributions

G.G.E. and A.D.O. conceived and designed research. G.G.E. and A.D.O. conducted experiments. C.B. and S.K. analyzed data. G.G.E. wrote the manuscript. All authors read and approved the manuscript.

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Funding

This study was supported by a grant from the Scientific Research Projects Foundation (BAP) of the Sakarya University of Turkey [Project No: 2016-08-06-031].