PMID- 31037974 OWN - NLM STAT- MEDLINE DCOM- 20200513 LR - 20200513 IS - 1532-7914 (Electronic) IS - 0163-5581 (Linking) VI - 71 IP - 8 DP - 2019 TI - Synergistic Effects of Nobiletin and Sorafenib Combination on Metastatic Prostate Cancer Cells. PG - 1299-1312 LID - 10.1080/01635581.2019.1601237 [doi] AB - 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. FAU - Guney Eskiler, Gamze AU - Guney Eskiler G AD - Department of Medical Biology Faculty of Medicine, Sakarya University , Sakarya , Turkey. FAU - Deveci, Asuman Ozkan AU - Deveci AO AUID- ORCID: 0000-0002-3248-4279 AD - Department of Medical Biology Faculty of Medicine, Sakarya University , Sakarya , Turkey. FAU - Bilir, Cemil AU - Bilir C AD - Department of Medical Oncology Faculty of Medicine, Sakarya University , Sakarya , Turkey. FAU - Kaleli, Suleyman AU - Kaleli S AD - Department of Medical Biology Faculty of Medicine, Sakarya University , Sakarya , Turkey. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190430 PL - United States TA - Nutr Cancer JT - Nutrition and cancer JID - 7905040 RN - 0 (Antioxidants) RN - 0 (Flavones) RN - 9ZOQ3TZI87 (Sorafenib) RN - D65ILJ7WLY (nobiletin) SB - IM MH - Antineoplastic Combined Chemotherapy Protocols/*pharmacology MH - Antioxidants/administration & dosage/pharmacology MH - Apoptosis/drug effects MH - Cell Proliferation/drug effects MH - Drug Synergism MH - Flavones/administration & dosage/*pharmacology MH - Humans MH - Male MH - Neoplasm Metastasis MH - PC-3 Cells MH - Prostatic Neoplasms/*drug therapy/pathology MH - Sorafenib/administration & dosage/*pharmacology EDAT- 2019/05/01 06:00 MHDA- 2020/05/14 06:00 CRDT- 2019/05/01 06:00 PHST- 2019/05/01 06:00 [pubmed] PHST- 2020/05/14 06:00 [medline] PHST- 2019/05/01 06:00 [entrez] AID - 10.1080/01635581.2019.1601237 [doi] PST - ppublish SO - Nutr Cancer. 2019;71(8):1299-1312. doi: 10.1080/01635581.2019.1601237. Epub 2019 Apr 30.