Lithium chloride has a biphasic effect on prostate cancer stem cells and a proportional effect on midkine levels

Erguven,Mine; Oktem,Gulperi; Kara,Ali Nail; Bilir,Ayhan

doi:10.3892/ol.2016.4946

Lithium chloride has a biphasic effect on prostate cancer stem cells and a proportional effect on midkine levels

Authors:
- Mine Erguven
- Gulperi Oktem
- Ali Nail Kara
- Ayhan Bilir
View Affiliations

Affiliations: Department of Medical Biochemistry, Faculty of Medicine, İstanbul Aydın University, Küçükçekmece 34295, İstanbul, Turkey, Department of Histology and Embryology, School of Medicine, Ege University, Bornova 35040, İzmir, Turkey, Department of Histology and Embryology, İstanbul Faculty of Medicine, İstanbul University, Capa 34390, İstanbul, Turkey, Department of Histology and Embryology, Emine‑Bahaeddin Nakıboğlu Faculty of Medicine, Zirve University, Gaziantep 27260, Turkey
Published online on: August 3, 2016 https://doi.org/10.3892/ol.2016.4946
Pages: 2948-2955

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Prostate cancer (PCa) is the second most frequent type of cancer in men worldwide and the levels of differentiation growth factor midkine (MK) are increased in PCa. Cancer and/or the treatment process itself may lead to psychiatric disorders. Lithium chloride (LiCl) has anti‑manic properties and has been used in cancer therapy; however, it has a queried safety profile. In addition, cancer stem cells are responsible for the heterogeneous phenotype of tumor cells; they are involved in progression, metastasis, recurrence and therapy resistance in various cancer types. The aims of the present study were to investigate the effect of different concentrations of LiCl on PCa stem cells (whether a shift from tumorigenic to non‑tumorigenic cells occurs) and to determine if these results can be explained through changes in MK levels. Monolayer and spheroid cultures of human prostate stem cells and non‑stem cells were incubated with low (1, 10 µM) and high (100, 500 µM) concentrations of LiCl for 72 h. Cell proliferation, apoptotic indices, MK levels and ultrastructure were evaluated. Cells stimulated with low concentrations showed high proliferation, low apoptotic indices, high MK levels and more healthy ultrastructure. Opposite results were obtained at high concentrations. Furthermore, stem cells were more sensitive to stimulation and more resistant to inhibition than non‑stem cells. LiCl exhibited concentration‑dependent effects on stem cell and non‑stem cell groups. MK levels were not involved in the biphasic effect of LiCl; however, they were proportionally affected. To the best of our knowledge, the present study was the first to show the effect of LiCl on PCa stem cells through MK.

View Figures

View References

1	Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 127:2893–2917. 2010. View Article : Google Scholar : PubMed/NCBI
2	Mavroudi M, Zarogoulidis P, Porpodis K, Kioumis I, Lampaki S, Yarmus L, Malecki R, Zarogoulidis K and Malecki M: Stem cells' guided gene therapy of cancer: New frontier in personalized and targeted therapy. J Cancer Res Ther (Manch). 2:22–33. 2014. View Article : Google Scholar : PubMed/NCBI
3	Boorjian SA, Eastham JA, Graefen M, Guillonneau B, Karnes RJ, Moul JW, Schaeffer EM, Stief C and Zorn KC: A critical analysis of the long-term impact of radical prostatectomy on cancer control and function outcomes. Eur Urol. 61:664–675. 2012. View Article : Google Scholar : PubMed/NCBI
4	Thompson I, Thrasher JB, Aus G, Burnett AL, CanbyHagino ED, Cookson MS, D'Amico AV, Dmochowski RR, Eton DT, Forman JD, et al: Guideline for the management of clinically localized prostate cancer: 2007 update. J Urol. 177:2106–2131. 2007. View Article : Google Scholar : PubMed/NCBI
5	Peitzsch C, Kurth I, KunzSchughart L, Baumann M and Dubrovska A: Discovery of the cancer stem cell related determinants of radioresistance. Radiother Oncol. 108:378–387. 2013. View Article : Google Scholar : PubMed/NCBI
6	Kreso A and Dick JE: Evolution of the cancer stem cell model. Cell Stem Cell. 14:275–291. 2014. View Article : Google Scholar : PubMed/NCBI
7	Kreso A, O'Brien CA, van Galen P, Gan OI, Notta F, Brown AM, Ng K, Ma J, Wienholds E, Dunant C, et al: Variable clonal repopulation dynamics influence chemotherapy response in colorectal cancer. Science. 339:543–548. 2013. View Article : Google Scholar : PubMed/NCBI
8	Kadomatsu K, Kishida S and Tsubota S: The heparin-binding growth factor midkine: The biological activities and candidate receptors. J Biochem. 153:511–521. 2013. View Article : Google Scholar : PubMed/NCBI
9	Muramatsu T and Kadomatsu K: Midkine: An emerging target of drug development for treatment of multiple diseases. Br J Pharmacol. 171:811–813. 2014. View Article : Google Scholar : PubMed/NCBI
10	Erguven M, Bilir A, Yazihan N, Ermis E, Sabanci A, Aktas E, Aras Y and Alpman V: Decreased therapeutic effects of noscapine combined with imatinib mesylate on human glioblastoma in vitro and the effect of midkine. Cancer Cell Int. 11:182011. View Article : Google Scholar : PubMed/NCBI
11	Zhao SL, Zhang YJ, Li MH, Zhang XL and Chen SL: Mesenchymal stem cells with overexpression of midkine enhance cell survival and attenuate cardiac dysfunction in a rat model of myocardial infarction. Stem Cell Res Ther. 5:372014. View Article : Google Scholar : PubMed/NCBI
12	Dai LC: Midkine translocated to nucleoli and involved in carcinogenesis. World J Gastroenterol. 15:412–416. 2009. View Article : Google Scholar : PubMed/NCBI
13	Takei Y, Kadomatsu K, Goto T and Muramatsu T: Combinational antitumor effect of siRNA against midkine and paclitaxel on growth of human prostate cancer xenografts. Cancer. 107:864–873. 2006. View Article : Google Scholar : PubMed/NCBI
14	Sakamoto K and Kadomatsu K: Midkine in the pathology of cancer, neural disease, and inflammation. Pathol Int. 62:445–455. 2012. View Article : Google Scholar : PubMed/NCBI
15	Suganthi M, Sangeetha G, Gayathri G and Ravi Sankar B: Biphasic dose-dependent effect of lithium chloride on survival of human hormone-dependent breast cancer cells (MCF-7). Biol Trace Elem Res. 150:477–486. 2012. View Article : Google Scholar : PubMed/NCBI
16	Peng Z, Ji Z, Mei F, Lu M, Ou Y and Cheng X: Lithium inhibits tumorigenic potential of PDA cells through targeting hedgehog-GLI signaling pathway. PLoS One. 8:e614572013. View Article : Google Scholar : PubMed/NCBI
17	Sabancι PA, Ergüven M, Yazιhan N, Aktaş E, Aras Y, Civelek E, Aydoseli A, Imer M, Gürtekin M and Bilir A: Sorafenib and lithium chloride combination treatment shows promising synergistic effects in human glioblastoma multiforme cells in vitro but midkine is not implicated. Neurol Res. 36:189–197. 2014. View Article : Google Scholar : PubMed/NCBI
18	Welshons WV, Engler KS, Taylor JA, Grady LH and Curran EM: Lithium-stimulated proliferation and alteration of phosphoinositide metabolites in MCF-7 human breast cancer cells. J Cell Physiol. 165:134–144. 1995. View Article : Google Scholar : PubMed/NCBI
19	Mann L, Heldman E, Shaltiel G, Belmaker RH and Agam G: Lithium preferentially inhibits adenylyl cyclase V and VII isoforms. Int J Neuropsychopharmacol. 11:533–539. 2008. View Article : Google Scholar : PubMed/NCBI
20	Santos LJ, Garcia JB, Pacheco JS, Vieira EB and Santos AM: Quality of life, pain, anxiety and depression in patients surgically treated with cancer of rectum. Arq Bras Cir Dig. 27:96–100. 2014.(In English, Portuguese). View Article : Google Scholar : PubMed/NCBI
21	Castillo V, Valenzuela R, Huidobro C, Contreras HR and Castellon EA: Functional characteristics of cancer stem cells and their role in drug resistance of prostate cancer. Int J Oncol. 45:985–994. 2014.PubMed/NCBI
22	Meacham CE and Morrison SJ: Tumour heterogeneity and cancer cell plasticity. Nature. 501:328–337. 2013. View Article : Google Scholar : PubMed/NCBI
23	Oktem G, Bilir A, Uslu R, Inan SV, Demiray SB, Atmaca H, Ayla S, Sercan O and Uysal A: Expression profiling of stem cell signaling alters with spheroid formation in CD133high/CD44high prostate cancer stem cells. Oncol Lett. 7:2103–2109. 2014.PubMed/NCBI
24	Bilir A, Erguven M, Ermis E, Sencan M and Yazihan N: Combination of imatinib mesylate with lithium chloride and medroxyprogesterone acetate is highly active in Ishikawa endometrial carcinoma in vitro. J Gynecol Oncol. 22:225–232. 2011. View Article : Google Scholar : PubMed/NCBI
25	Hossein G, Zavareh VA and Fard PS: Combined treatment of androgen-independent prostate cancer cell line DU145 with chemotherapeutic agents and lithium chloride: Effect on growth arrest and/or apoptosis. Avicenna J Med Biotechnol. 4:75–87. 2012.PubMed/NCBI
26	AzimianZavareh V, Hossein G and Janzamin E: Effect of lithium chloride and antineoplastic drugs on survival and cell cycle of androgen-dependent prostate cancer LNCap cells. Indian J Pharmacol. 44:714–721. 2012. View Article : Google Scholar : PubMed/NCBI
27	Tang DG: Understanding cancer stem cell heterogeneity and plasticity. Cell Res. 22:457–472. 2012. View Article : Google Scholar : PubMed/NCBI
28	Gupta PB, Fillmore CM, Jiang G, Shapira SD, Tao K, Kuperwasser C and Lander ES: Stochastic state transitions give rise to phenotypic equilibrium in populations of cancer cells. Cell. 146:633–644. 2011. View Article : Google Scholar : PubMed/NCBI
29	Cojoc M, Mäbert K, Muders MH and Dubrovska A: A role for cancer stem cells in therapy resistance: Cellular and molecular mechanisms. Semin Cancer Biol. 31:16–27. 2015. View Article : Google Scholar : PubMed/NCBI
30	Takebe N and Ivy SP: Controversies in cancer stem cells: Targeting embryonic signaling pathways. Clin Cancer Res. 16:3106–3112. 2010. View Article : Google Scholar : PubMed/NCBI
31	Visvader JE and Lindeman GJ: Cancer stem cells in solid tumours: Accumulating evidence and unresolved questions. Nat Rev Cancer. 8:755–768. 2008. View Article : Google Scholar : PubMed/NCBI
32	Wang XK, He JH, Xu JH, Ye S, Wang F, Zhang H, Huang ZC, To KK and Fu LW: Afatinib enhances the efficacy of conventional chemotherapeutic agents by eradicating cancer stem-like cells. Cancer Res. 74:4431–4445. 2014. View Article : Google Scholar : PubMed/NCBI
33	Polyak K and Weinberg RA: Transitions between epithelial and mesenchymal states: Acquisition of malignant and stem cell traits. Nat Rev Cancer. 9:265–273. 2009. View Article : Google Scholar : PubMed/NCBI
34	Carrasco E, Alvarez PJ, Prados J, Melguizo C, Rama AR, Aránega A and Rodríguez-Serrano F: Cancer stem cells and their implication in breast cancer. Eur J Clin Invest. 44:678–687. 2014. View Article : Google Scholar : PubMed/NCBI
35	Kahn M: Can we safely target the WNT pathway? Nat Rev Drug Discov. 13:513–532. 2014. View Article : Google Scholar : PubMed/NCBI
36	Silva AK, Yi H, Hayes SH, Seigel GM and Hackam AS: Lithium chloride regulates the proliferation of stem-like cells in retinoblastoma cell lines: A potential role for the canonical Wnt signaling pathway. Mol Vis. 16:36–45. 2010.PubMed/NCBI
37	Cai C and Zhu X: The Wnt/β-catenin pathway regulates self-renewal of cancer stem-like cells in human gastric cancer. Mol Med Rep. 5:1191–1196. 2012.PubMed/NCBI
38	Teng Y, Wang X, Wang Y and Ma D: Wnt/beta-catenin signaling regulates cancer stem cells in lung cancer A549 cells. Biochem Biophys Res Commun. 392:373–379. 2010. View Article : Google Scholar : PubMed/NCBI
39	Sun JL, Chen DL, Hu ZQ, Xu YZ, Fang HS, Wang XY, Kan L and Wang SY: Arsenite promotes intestinal tumor cell proliferation and invasion by stimulating epithelial-to-mesenchymal transition. Cancer Biol Ther. 15:1312–1319. 2014. View Article : Google Scholar : PubMed/NCBI
40	Sottoriva A, Spiteri I, Piccirillo SG, Touloumis A, Collins VP, Marioni JC, Curtis C, Watts C and Tavaré S: Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics. Proc Natl Acad Sci USA. 110:4009–4014. 2013. View Article : Google Scholar : PubMed/NCBI