Suat Erdogan1, Riza Serttas2, Kader Turkekul2, Ilker Dibirdik3. 1. Department of Medical Biology, School of Medicine, Trakya University, Balkan Campus, Edirne, Turkey. suaterdogan@trakya.edu.tr. 2. Department of Medical Biology, School of Medicine, Trakya University, Balkan Campus, Edirne, Turkey. 3. Department of Biochemistry, School of Medicine, Trakya University, Balkan Campus, Edirne, Turkey.
Abstract
BACKGROUND: Tumor-initiating or cancer stem cells (CSCs) reduce the effectiveness of conventional therapy. Thus, it is crucial to eliminate CSCs while killing bulky cancer cells using a combination of conventional chemotherapy and anti-CSC drugs. Salinomycin is a selective inhibitor against CSCs and shows promise in combination applications. The aim of the study was to examine the efficacy of co-administered cabazitaxel and salinomycin on the survival of prostate cancer cells and CSCs. METHODS AND RESULTS: CD44 + stem cells were isolated from human PC3 prostate cancer cells by using magnetic activated cell sorting. The cells were concomitantly exposed to salinomycin and cabazitaxel, and the cell survival was determined by MTT test. Apoptosis was assessed by image-based cytometer, and cell migration was evaluated by wound healing assay. The expression of target mRNA and protein were assessed by RT-qPCR and Western blot, respectively. Combination index (CI) analysis showed that simultaneous administration of salinomycin and cabazitaxel was able to exert strong synergistic effect on CD44 + subpopulation (CI = 0.33), but no synergism was observed in PC3 cells. The combination of the two agents significantly increased Bax, cytochrome c, caspase-3 and - 8 mRNA expression in CD44 + CSCs, causing apoptosis. The applied therapy strategy strongly inhibited the phosphorylation of Akt, protein expression of Akt1, NF-κB and Wnt. CONCLUSIONS: In conclusion, our data suggest that combining salinomycin with cabazitaxel shows promise as a prostate cancer treatment approach that can target CSCs.
BACKGROUND: Tumor-initiating or cancer stem cells (CSCs) reduce the effectiveness of conventional therapy. Thus, it is crucial to eliminate CSCs while killing bulky cancer cells using a combination of conventional chemotherapy and anti-CSC drugs. Salinomycin is a selective inhibitor against CSCs and shows promise in combination applications. The aim of the study was to examine the efficacy of co-administered cabazitaxel and salinomycin on the survival of prostate cancer cells and CSCs. METHODS AND RESULTS: CD44 + stem cells were isolated from human PC3 prostate cancer cells by using magnetic activated cell sorting. The cells were concomitantly exposed to salinomycin and cabazitaxel, and the cell survival was determined by MTT test. Apoptosis was assessed by image-based cytometer, and cell migration was evaluated by wound healing assay. The expression of target mRNA and protein were assessed by RT-qPCR and Western blot, respectively. Combination index (CI) analysis showed that simultaneous administration of salinomycin and cabazitaxel was able to exert strong synergistic effect on CD44 + subpopulation (CI = 0.33), but no synergism was observed in PC3 cells. The combination of the two agents significantly increased Bax, cytochrome c, caspase-3 and - 8 mRNA expression in CD44 + CSCs, causing apoptosis. The applied therapy strategy strongly inhibited the phosphorylation of Akt, protein expression of Akt1, NF-κB and Wnt. CONCLUSIONS: In conclusion, our data suggest that combining salinomycin with cabazitaxel shows promise as a prostate cancer treatment approach that can target CSCs.
Authors: Yunsheng Zhang; Luogen Liu; Fang Li; Tao Wu; Hongtao Jiang; Xianxun Jiang; Xiaobo Du; Yi Wang Journal: Biomed Res Int Date: 2017-06-06 Impact factor: 3.411
Authors: Annika Fendler; Daniel Bauer; Jonas Busch; Klaus Jung; Annika Wulf-Goldenberg; Severine Kunz; Kun Song; Adam Myszczyszyn; Sefer Elezkurtaj; Bettina Erguen; Simone Jung; Wei Chen; Walter Birchmeier Journal: Nat Commun Date: 2020-02-17 Impact factor: 14.919