Email this article 
The comparative assessment of single dose versus co-administration of salinomycin and MK-2206 on viability, apoptosis, and gene expression of human prostate cancer cells
Abstract
Globally, the most prevalent medical condition affecting males is identified as prostate cancer (PCa). The aim of the present study was the comparative assessment of single dose versus co-administration of salinomycin and MK-2206 on several laboratory indicators of PCa. The probable anticancer potential of salinomycin and MK-2206 was assessed in a panel of PCa cell line. Several experiments were conducted to determine the primary underlying biological processes, which includes apoptosis induction, cancer cell survival, and gene expression count data. As compared to the negative control group, all salinomycin, MK-2206, and salinomycin + MK-2206 treatment groups showed significantly lower rates of cell viability, and both Akt and Bcl-2 expressions [(P <0.001), (P <0.001), and (P <0.001), respectively]. In addition, treatments with salinomycin, MK-2206, and salinomycin + MK-2206 was accompanied by noticeably higher level of apoptosis in PCa cells in comparison with the negative control group. Specifically, the concomitant use of salinomycin + MK-2206 resulted in synergistic advantages in the study experiments. Given that timely treatment is widely believed to play an important role in management of the PCa, our data suggest that salinomycin and MK-2206 therapy may be considered as a suitable strategy for PCa improvements. Thus, further clinical trial studies are required in order to obtain stronger evidence regarding the effectiveness of salinomycin and MK-2206 treatments in PCa.
Keywords
Full Text:
Supplementary filesReferences
Swami U, McFarland T, Nussenzveig R, Agarwal N. Advanced Prostate Cancer: Treatment Advances and Future Directions. Trends Cancer. 2020; 6(8):702-15.
Li J, Xu C, Lee HJ, Ren S, Zi X, Zhang Z, et al. A genomic and epigenomic atlas of prostate cancer in Asian populations. Nature. 2020; 580(7801):93-9.
Ma Y, Sender S, Sekora A, Kong W, Bauer P, Ameziane N, et al. The inhibitory response to PI3K/AKT pathway inhibitors MK-2206 and Buparlisib is related to genetic differences in pancreatic ductal adenocarcinoma cell lines. Int J Mol Sci. 2022; 23(8):4295.
Sangai T, Akcakanat A, Chen H, Tarco E, Wu Y, Do K-A, et al. Biomarkers of Response to Akt Inhibitor MK-2206 in Breast CancerAntitumor Activity of MK-2206. Clin Cancer Res. 2012; 18(20):5816-28.
Iida M, Harari P, Wheeler D, Toulany M. Targeting AKT/PKB to improve treatment outcomes for solid tumors. Mutat Res. 2020; 819-820:111690.
Pérez-Gracia JL, Gúrpide A, de Fata Chillón F, Villacampa F. The role of chemotherapy in the treatment of hormone sensitive metastatic prostate cancer. Arch Esp Urol. 2018; 71(3):276-80.
Rizzo A, Mollica V, Cimadamore A, Santoni M, Scarpelli M, Giunchi F, et al. Is there a role for immunotherapy in prostate cancer? Cells. 2020; 9(9):2051.
Teo MY, Rathkopf DE, Kantoff P. Treatment of advanced prostate cancer. Annu Rev Med. 2019; 70:479-499.
Oun R, Moussa YE, Wheate NJ. The side effects of platinum-based chemotherapy drugs: a review for chemists. Dalton trans. 2018; 47(19):6645-6653.
Prakash O, Kumar A, Kumar P. Anticancer potential of plants and natural products. Am J Pharmacol Sci. 2013; 1(6):104-15.
Ma BB, Lui VW, Hui CW, Lau CP, Wong C-H, Hui EP, et al. Preclinical evaluation of the AKT inhibitor MK-2206 in nasopharyngeal carcinoma cell lines. Invest New Drugs. 2013; 31(3):567-75.
Meng J, Dai B, Fang B, Bekele BN, Bornmann WG, Sun D, et al. Combination treatment with MEK and AKT inhibitors is more effective than each drug alone in human non-small cell lung cancer in vitro and in vivo. PloS one. 2010; 5(11):e14124.
Ji S, Lin W, Wang L, Ni Z, Jin F, Zha X, et al. Combined targeting of mTOR and Akt using rapamycin and MK-2206 in the treatment of tuberous sclerosis complex. J Cancer. 2017; 8(4):555-562.
Dewangan J, Srivastava S, Rath SK. Salinomycin: A new paradigm in cancer therapy. Tumor Biol. 2017; 39(3):1010428317695035.
Huczyński A, Janczak J, Antoszczak M, Wietrzyk J, Maj E, Brzezinski B. Antiproliferative activity of salinomycin and its derivatives. Bioorg Med Chem Lett. 2012; 22(23):7146-50.
Kim K-Y, Yu S-N, Lee S-Y, Chun S-S, Choi Y-L, Park Y-M, et al. Salinomycin-induced apoptosis of human prostate cancer cells due to accumulated reactive oxygen species and mitochondrial membrane depolarization. Biochem Biophys Res Commun. 2011; 413(1):80-6.
Riccioni R, Dupuis ML, Bernabei M, Petrucci E, Pasquini L, Mariani G, et al. The cancer stem cell selective inhibitor salinomycin is a p-glycoprotein inhibitor. Blood Cells Mol Dis. 2010; 45(1):86-92.
Choi A-R, Kim J-H, Yoon S. Sensitization of cancer cells through reduction of total Akt and downregulation of salinomycin-induced pAkt, pGSk3β, pTSC2, and p4EBP1 by cotreatment with MK-2206. Biomed Res Int. 2014;2014:295760.
Arikawa E, Sun Y, Wang J, Zhou Q, Ning B, Dial SL, et al. Cross-platform comparison of SYBR® Green real-time PCR with TaqMan PCR, microarrays and other gene expression measurement technologies evaluated in the MicroArray Quality Control (MAQC) study. BMC Genomics. 2008; 9:328.
Nozari E, Moradi A, Samadi M. Effect of atorvastatin, curcumin, and quercetin on miR-21 and miR-122 and their correlation with TGFβ1 expression in experimental liver fibrosis. Life Sci. 2020; 259:118293.
Huang D, Wang F, Wu W, Lian C, Liu E. MicroRNA-429 inhibits cancer cell proliferation and migration by targeting the AKT1 in melanoma. Cancer Biomark. 2019; 26(1):63-8.
AlMalki FA, Hassan AM, Klaab ZM, Abdulla S, Pizzi A. Tannin Nanoparticles (NP99) Enhances the Anticancer Effect of Tamoxifen on ER [supercript]+[/supercript] Breast Cancer Cells. J Renew Mater. 2021; 9(12):2077-92.
Liu B, Sun X. miR-25 promotes invasion of human non-small cell lung cancer via CDH1. Bioengineered. 2019; 10(1):271-81.
Al-Bazz YO, Underwood JC, Brown BL, Dobson PR. Prognostic significance of Akt, phospho-Akt and BAD expression in primary breast cancer. Eur J Cancer. 2009; 45(4):694-704.
Zhou L, Zhao Y. B7-H3 induces ovarian cancer drugs resistance through an PI3K/AKT/BCL-2 signaling pathway. Cancer Manag Res. 2019; 11:10205-10214.
Balasis ME, Forinash KD, Chen YA, Fulp WJ, Coppola D, Hamilton AD, et al. Combination of farnesyltransferase and Akt inhibitors is synergistic in breast cancer cells and causes significant breast tumor regression in ErbB2 transgenic mice. Clin Cancer Res. 2011; 17(9):2852-62.
Cheng Y, Zhang Y, Zhang L, Ren X, Huber-Keener KJ, Liu X, et al. MK-2206, a Novel Allosteric Inhibitor of Akt, Synergizes with Gefitinib against Malignant Glioma via Modulating Both Autophagy and ApoptosisSynergistic Antitumor Effect of MK-2206 and Gefitinib. Mol Cancer Ther. 2012; 11(1):154-64.
Chen K-F, Chen H-L, Tai W-T, Feng W-C, Hsu C-H, Chen P-J, et al. Activation of phosphatidylinositol 3-kinase/Akt signaling pathway mediates acquired resistance to sorafenib in hepatocellular carcinoma cells. J Pharmacol Exp Ther. 2011; 337(1):155-61.
Neri L, Cani A, Martelli A, Simioni C, Junghanss C, Tabellini G, et al. Targeting the PI3K/Akt/mTOR signaling pathway in B-precursor acute lymphoblastic leukemia and its therapeutic potential. Leukemia. 2014; 28(4):739-48.
Kim J-H, Choi A-R, Kim YK, Kim HS, Yoon S. Low amount of salinomycin greatly increases Akt activation, but reduces activated p70S6K levels. Int J Mol Sci. 2013; 14(9):17304-18.
Ketola K, Hilvo M, Hyötyläinen T, Vuoristo A, Ruskeepää A-L, Orešič M, et al. Salinomycin inhibits prostate cancer growth and migration via induction of oxidative stress. Br J Cancer. 2012; 106(1):99-106.
Mao J, Fan S, Ma W, Fan P, Wang B, Zhang J, et al. Roles of Wnt/β-catenin signaling in the gastric cancer stem cells proliferation and salinomycin treatment. Cell Death Dis. 2014; 5(1):e1039.
Li T, Su L, Zhong N, Hao X, Zhong D, Singhal S, et al. Salinomycin induces cell death with autophagy through activation of endoplasmic reticulum stress in human cancer cells. Autophagy. 2013; 9(7):1057-68.
Refbacks
- There are currently no refbacks.
Copyright (c) 2023 © The Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.