Volume 11, Issue 1 (Vol.11 No.1 Apr 2022)                   rbmb.net 2022, 11(1): 157-165 | Back to browse issues page

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Savaee M, Bakhshi A, Yaghoubi F, Pourrajab F, Goodarzvand Chegini K. Evaluating the Effects of Separate and Concomitant Use of MK-2206 and Salinomycin on Prostate Cancer Cell Line. rbmb.net. 2022; 11 (1) :157-165
URL: http://rbmb.net/article-1-841-en.html
Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Abstract:   (592 Views)
Background: Prostate cancer is known as one of the most prevalent health disorders in the male population globally. The aim of the current study was to evaluate the effects of separate and concomitant use of MK-2206 and salinomycin on prostate cancer cell line.

 Methods: The antitumor potential of separate and concomitant use of MK-2206 and salinomycin was evaluated in a panel of prostate cancer cell line (PC-3). To get insights into the underlying mechanism of action, different assays including the rate of apoptosis, cell viability, and gene expression were performed in treated prostate cancer cells.

Results: A significant reduction was detected in the viability percentage of prostate cancer cells (p< 0.001) and the rate of Akt expression (p< 0.001) in all salinomycin, MK-2206, and salinomycin+MK-2206 groups compared to the negative control group. Furthermore, in comparison with the negative control group, there was a notable increase in both the rate of Bad expression (p< 0.001) and prostate cancer cells apoptosis after salinomycin, MK-2206, and salinomycin+MK-2206 treatments. Moreover, the concomitant use of salinomycin+MK-2206 revealed synergistic improvements regarding the viability of prostate cancer cells and the rate of the Akt and Bad expressions compared to the separate administration of salinomycin and MK-2206 (all p< 0.05).

Conclusions: The findings of the present study may contribute to improving the efficacy of the therapies regarding the management of prostate cancer and providing a beneficial strategy in clinical trials.
Full-Text [PDF 321 kb]   (309 Downloads)    
Type of Article: Original Article | Subject: Cell Biology
Received: 2021/12/23 | Accepted: 2021/12/25 | Published: 2022/05/26

1. Barani M, Sabir F, Rahdar A, Arshad R, Kyzas GZ. Nanotreatment and nanodiagnosis of prostate cancer: recent updates. Nanomaterials (Basel). 2020;10(9):1696. [DOI:10.3390/nano10091696] [PMID] [PMCID]
2. Fujita K, Hayashi T, Matsushita M, Uemura M, Nonomura N. Obesity, inflammation, and prostate cancer. J Clin Med. 2019;8(2):201. [DOI:10.3390/jcm8020201] [PMID] [PMCID]
3. Chen S, Huang V, Xu X, Livingstone J, Soares F, Jeon J, et al. Widespread and functional RNA circularization in localized prostate cancer. Cell. 2019;176(4):831-843. [DOI:10.1016/j.cell.2019.01.025] [PMID]
4. Mei W, Lin X, Kapoor A, Gu Y, Zhao K, Tang D. The contributions of prostate cancer stem cells in prostate cancer initiation and metastasis. Cancers (Basel). 2019;11(4):434. [DOI:10.3390/cancers11040434] [PMID] [PMCID]
5. 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):276-280.
6. Dyrstad SW, Shah P, Rao K. Chemotherapy for prostate cancer. Current pharmaceutical design. 2006;12(7):819-37. [DOI:10.2174/138161206776056100] [PMID]
7. 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. [DOI:10.3390/cells9092051] [PMID] [PMCID]
8. 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. [DOI:10.1039/C8DT00838H] [PMID]
9. Lawania RD, Mishra A. Anticancer potential of plants and natural products: a review. Journal of Diagnostic Techniques and Biomedical Analysis. 2017;2013.
10. Hirai H, Sootome H, Nakatsuru Y, Miyama K, Taguchi S, Tsujioka K, et al. MK-2206, an allosteric Akt inhibitor, enhances antitumor efficacy by standard chemotherapeutic agents or molecular targeted drugs in vitro and in vivo. Mol Cancer Ther. 2010;9(7):1956-67. [DOI:10.1158/1535-7163.MCT-09-1012] [PMID]
11. 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 cancer. Clin Cancer Res. 2012;18(20):5816-28. [DOI:10.1158/1078-0432.CCR-12-1141] [PMID] [PMCID]
12. Dong Y, Gong W, Hua Z, Chen B, Zhao G, Liu Z, et al. Combination of Rapamycin and MK-2206 induced cell death via autophagy and Necroptosis in MYCN-amplified neuroblastoma cell lines. Front Pharmacol. 2020;11:31. [DOI:10.3389/fphar.2020.00031] [PMID] [PMCID]
13. Djuzenova CS, Fiedler V, Memmel S, Katzer A, Sisario D, Brosch PK, et al. Differential effects of the Akt inhibitor MK-2206 on migration and radiation sensitivity of glioblastoma cells. BMC cancer. 2019;19(1):1-18. [DOI:10.1186/s12885-019-5517-4] [PMID] [PMCID]
14. Gorlick R, Maris JM, Houghton PJ, Lock R, Carol H, Kurmasheva RT, et al. Testing of the Akt/PKB inhibitor MK‐2206 by the pediatric preclinical testing program. Pediatric blood & cancer. 2012;59(3):518-24. [DOI:10.1002/pbc.23412] [PMID] [PMCID]
15. Yu J, Yang Y, Li S, Meng P. Salinomycin triggers prostate cancer cell apoptosis by inducing oxidative and endoplasmic reticulum stress via suppressing Nrf2 signaling. Exp Ther Med. 2021;22(3):946. [DOI:10.3892/etm.2021.10378] [PMID] [PMCID]
16. 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. Biochemical and biophysical research communications. 2011;413(1):80-86. [DOI:10.1016/j.bbrc.2011.08.054] [PMID]
17. 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 research international. 2014;2014. [DOI:10.1155/2014/295760] [PMID] [PMCID]
18. 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. [DOI:10.1186/1471-2164-9-328] [PMID] [PMCID]
19. 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. [DOI:10.1016/j.lfs.2020.118293] [PMID]
20. 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. [DOI:10.1016/j.ejca.2008.11.044] [PMID]
21. Smith AJ, Karpova Y, D'Agostino Jr R, Willingham M, Kulik G. Expression of the Bcl-2 protein BAD promotes prostate cancer growth. PLoS One. 2009;4(7):e6224. [DOI:10.1371/journal.pone.0006224] [PMID] [PMCID]
22. 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):2852-2862. [DOI:10.1158/1078-0432.CCR-10-2544] [PMID] [PMCID]
23. 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 apoptosis. Mol Cancer Ther. 2012;11(1):154-64. [DOI:10.1158/1535-7163.MCT-11-0606] [PMID] [PMCID]
24. 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. [DOI:10.1124/jpet.110.175786] [PMID]
25. Neri LM, 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. [DOI:10.1038/leu.2013.226] [PMID]
26. Parajuli B, Lee H-G, Kwon S-H, Cha S-D, Shin S-J, Lee G-H, et al. Salinomycin inhibits Akt/NF-κB and induces apoptosis in cisplatin resistant ovarian cancer cells. Cancer Epidemiol. 2013;37(4):512-7. [DOI:10.1016/j.canep.2013.02.008] [PMID]
27. 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. [DOI:10.3390/ijms140917304] [PMID] [PMCID]
28. 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. British journal of cancer. 2012;106(1):99-106. [DOI:10.1038/bjc.2011.530] [PMID] [PMCID]
29. 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 & disease. 2014;5(1):e1039-e. [DOI:10.1038/cddis.2013.515] [PMID] [PMCID]
30. 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. [DOI:10.4161/auto.24632] [PMID] [PMCID]

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