Estradiol induces JNK-dependent apoptosis in glioblastoma cells

Altiok,Nedret; Ersoz,Melike; Koyuturk,Meral

doi:10.3892/ol.2011.385

Estradiol induces JNK-dependent apoptosis in glioblastoma cells

Authors:
- Nedret Altiok
- Melike Ersoz
- Meral Koyuturk
View Affiliations

Affiliations: Yeni Yuzyil University School of Medicine, Department of Pharmacology, Cevizlibag-Topkapi, Istanbul, Turkey, Institute of Medical Sciences, Istanbul Science/Bilim University, Istanbul, Turkey, Department of Histology and Embryology of Istanbul Science/Bilim University, Istanbul, Turkey
Published online on: August 17, 2011 https://doi.org/10.3892/ol.2011.385
Pages: 1281-1285

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

Estrogens exert multiple regulatory actions on cellular events in a variety of tissues including the brain. In the present study, the signaling mechanisms of the concentration‑dependent effects of 17-β-estradiol (estradiol) on glioblastoma cells were investigated. Cell viability was evaluated by the trypan blue exclusion assay. Cell growth and kinase activities were evaluated by immunocytochemistry and Western blotting. The results showed that high concentrations of estradiol inhibit growth and induce apoptosis in C6 rat glioma and T98G human glioblastoma cells. The blockade of the c-jun NH2-terminal kinase (JNK) signaling pathway prevented these effects of estradiol, indicating the critical role of the JNK/c-jun signaling cascade in glioblastoma cell growth inhibition and cell death in response to high concentrations of estradiol. Collectively, these findings highlight the potential of new discoveries in sensitizing estrogen-sensitive tumors to chemotherapeutic drugs, and may lead to the development of new JNK-based effective therapies.

View Figures

View References

1	Minniti G, Muni R, Lanzetta G, Marchetti P and Enrici RM: Chemotherapy for glioblastoma: current treatment and future perspectives for cytotoxic and targeted agents. Anticancer Res. 29:5171–5184. 2009.PubMed/NCBI
2	Quick A, Patel D, Hadziahmetovic M, Chakravarti A and Mehta M: Current therapeutic paradigms in glioblastoma. Rev Recent Clin Trials. 5:14–27. 2010. View Article : Google Scholar : PubMed/NCBI
3	Lino M and Merlo A: Translating biology into clinic: the case of glioblastoma. Curr Opin Cell Biol. 21:311–316. 2009. View Article : Google Scholar : PubMed/NCBI
4	Yague JG, Lavaque E, Carretero J, Azcoitia I and Garcia-Segura LM: Aromatase, the enzyme responsible for estrogen biosynthesis, is expressed by human and rat glioblastomas. Neurosci Lett. 368:279–284. 2004. View Article : Google Scholar : PubMed/NCBI
5	Sribnick EA, Ray SK and Banik NL: Estrogen prevents glutamate-induced apoptosis in C6 glioma cells by a receptor-mediated mechanism. Neuroscience. 137:197–209. 2006. View Article : Google Scholar
6	Hui AM, Zhang W, Chen W, Xi D, Purow B, Friedman GC and Fine HA: Agents with selective estrogen receptor (ER) modulator activity induce apoptosis in vitro and in vivo in ER-negative glioma cells. Cancer Res. 64:9115–9123. 2004. View Article : Google Scholar : PubMed/NCBI
7	Moodbidri MS and Shirsat NV: Activated JNK brings about accelerated apoptosis of Bcl-2-overexpressing C6 glioma cells on treatment with tamoxifen. J Neurochem. 92:1–9. 2005. View Article : Google Scholar : PubMed/NCBI
8	Tian F, Wu H, Li Z, Wang N, Huang J, Li C and Xie F: Activated PKCalpha/ERK1/2 signaling inhibits tamoxifen-induced apoptosis in C6 cells. Cancer Invest. 27:802–808. 2009. View Article : Google Scholar : PubMed/NCBI
9	Altiok N, Koyuturk M and Altiok S: JNK pathway regulates estradiol-induced apoptosis in hormone-dependent human breast cancer cells. Breast Cancer Res Treat. 105:247–254. 2007. View Article : Google Scholar : PubMed/NCBI
10	McCarthy MM: The two faces of estradiol: effects on the developing brain. Neuroscientist. 15:599–610. 2009. View Article : Google Scholar : PubMed/NCBI
11	Waters EM and Simerly RB: Estrogen induces caspase-dependent cell death during hypothalamic development. J Neurosci. 29:9714–9718. 2009. View Article : Google Scholar : PubMed/NCBI
12	Lewis-Wambi JS and Jordan VC: Estrogen regulation of apoptosis: how can one hormone stimulate and inhibit? Breast Cancer Res. 11:2062009. View Article : Google Scholar : PubMed/NCBI
13	Bennett BL, Sasaki DT, Murray BW, O’Leary EC, Sakata ST, Xu W, Leisten JC, Motiwala A, Pierce S, Satoh Y, Bhagwat SS, Manning AM and Anderson DW: SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase. Proc Natl Acad Sci USA. 98:13681–13686. 2001. View Article : Google Scholar : PubMed/NCBI
14	Prieto LM, Brown JW, Perez-Stable C and Fishman LM: High dose 17 beta-estradiol and the alpha-estrogen agonist PPT trigger apoptosis in human adrenal carcinoma cells but the beta-estrogen agonist DPN does not. Horm Metab Res. 40:311–314. 2008. View Article : Google Scholar : PubMed/NCBI
15	Pozzi S, Benedusi V, Maggi A and Vegeto E: Estrogen action in neuroprotection and brain inflammation. Ann N Y Acad Sci. 1089:302–323. 2006. View Article : Google Scholar : PubMed/NCBI
16	Morissette M, Le Saux M, D’Astous M, Jourdain S, Al Sweidi S, Morin N, Estrada-Camerana E, Mendez P, Garcia-Segura LM and Di Paolo T: Contribution of estrogen receptors alpha and beta to the effects of estradiol in the brain. J Steroid Biochem Mol Biol. 108:327–338. 2008. View Article : Google Scholar : PubMed/NCBI
17	Raz L, Khan MM, Mahesh VB, Vadlamudi RK and Brann DW: Rapid estrogen signaling in the brain. Neurosignals. 16:140–153. 2008. View Article : Google Scholar : PubMed/NCBI
18	Levin ER: Plasma membrane estrogen receptors. Trends Endocrinol Metab. 20:477–482. 2009. View Article : Google Scholar
19	Waetzig V and Herdegen T: Context-specific inhibition of JNKs: overcoming the dilemma of protection and damage. Trends Pharmacol Sci. 26:455–461. 2005.PubMed/NCBI
20	Björkblom B, Vainio JC, Hongisto V, Herdegen T, Courtney MJ and Coffey ET: All JNKs can kill, but nuclear localization is critical for neuronal death. J Biol Chem. 283:19704–19713. 2008.PubMed/NCBI
21	Mhaidat NM, Zhang XD, Jiang CC and Hersey P: Docetaxel-induced apoptosis of human melanoma is mediated by activation of c-Jun NH2-terminal kinase and inhibited by the mitogen-activated protein kinase extracellular signal-regulated kinase 1/2 pathway. Clin Cancer Res. 13:1308–1314. 2007. View Article : Google Scholar
22	Kolomeichuk SN, Terrano DT, Lyle CS, Sabapathy K and Chambers TC: Distinct signaling pathways of microtubule inhibitors - vinblastine and Taxol induce JNK-dependent cell death but through AP-1-dependent and AP-1-independent mechanisms, respectively. FEBS J. 275:1889–1899. 2008. View Article : Google Scholar
23	Lagadinou ED, Ziros PG, Tsopra OA, Dimas K, Kokkinou D, Thanopoulou E, Karakantza M, Pantazis P, Spyridonidis A and Zoumbos NC: c-Jun N-terminal kinase activation failure is a new mechanism of anthracycline resistance in acute myeloid leukemia. Leukemia. 22:1899–1908. 2008. View Article : Google Scholar : PubMed/NCBI
24	Zerp SF, Stoter R, Kuipers G, Yang D, Lippman ME, van Blitterswijk WJ, Bartelink H, Rooswinkel R, Lafleur V and Verheij M: AT-101, a small molecule inhibitor of anti-apoptotic Bcl-2 family members, activates the SAPK/JNK pathway and enhances radiation-induced apoptosis. Radiat Oncol. 4:472009. View Article : Google Scholar : PubMed/NCBI
25	Kan Z, Jaiswal BS, Stinson J, Janakiraman V, Bhatt D, Stern HM, Yue P, Haverty PM, Bourgon R, Zheng J, Moorhead M, Chaudhuri S, Tomsho LP, Peters BA, Pujara K, Cordes S, Davis DP, Carlton VE, Yuan W, Li L, Wang W, Eigenbrot C, Kaminker JS, Eberhard DA, Waring P, Schuster SC, Modrusan Z, Zhang Z, Stokoe D, de Sauvage FJ, Faham M and Seshagiri S: Diverse somatic mutation patterns and pathway alterations in human cancers. Nature. 466:869–73. 2010. View Article : Google Scholar : PubMed/NCBI
26	Tricker E, Arvand A, Kwan R, Chen GY, Gallagher E and Cheng G: Apoptosis induced by cytoskeletal disruption requires distinct domains of MEKK1. PLoS One. 6:e173102011. View Article : Google Scholar : PubMed/NCBI