Corticosterone inhibits the expression of cannabinoid receptor‑1 and cannabinoid receptor agonist‑induced decrease in cell viability in glioblastoma cells

Sugimoto,Naotoshi; Ishibashi,Hiroaki; Ueda,Yoshibumi; Nakamura,Hiroyuki; Yachie,Akihiro; Ohno‑Shosaku,Takako

doi:10.3892/ol.2019.10456

Corticosterone inhibits the expression of cannabinoid receptor‑1 and cannabinoid receptor agonist‑induced decrease in cell viability in glioblastoma cells

Authors:
- Naotoshi Sugimoto
- Hiroaki Ishibashi
- Yoshibumi Ueda
- Hiroyuki Nakamura
- Akihiro Yachie
- Takako Ohno‑Shosaku
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Affiliations: Department of Physiology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa 920‑8640, Japan, Department of Oral and Maxillofacial Surgery, Kanazawa Medical University, Uchinada, Ishikawa 920‑0293, Japan, Department of General Systems Studies, Graduate School of Arts and Sciences, University of Tokyo, Tokyo 153‑8902, Japan, Department of Public Health, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa 920‑8640, Japan, Department of Pediatrics, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa 920‑8640, Japan, Faculty of Health Sciences, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa 920‑0942, Japan
Published online on: June 7, 2019 https://doi.org/10.3892/ol.2019.10456
Pages: 1557-1563

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Abstract

The endocannabinoid system regulates physiological and pathological conditions, including inflammation and cancer. Recently, emotional and physical stressors were observed to be involved in impairing the endocannabinoid system, which was concomitant with an increase in serum corticosteroids. However, the influence of corticosteroids on the endocannabinoid system has yet to be completely elucidated. The present study investigated the effects of corticosterone, one of the corticosteroids, on the endocannabinoid system in malignant glioblastoma cells in vitro. U‑87 MG cells derived from malignant glioblastoma were subjected to corticosterone stimulation and their viability, signal transduction, and endocannabinoid‑related gene expression were examined. Corticosterone decreased the mRNA and protein expressions of cyclooxygenase‑2. Of note, although endocannabinoids decreased cell viability, corticosterone inhibited the cannabinoid receptor agonist‑induced decrease in cell viability by downregulating the mRNA and protein expressions of cannabinoid receptor 1 (CB1) in glioblastoma cells. These results suggest that corticosteroids modify the endocannabinoid system in glioblastoma cells, and a reduction in the beneficial anti‑tumor effects of endocannabinoids through downregulation of the CB1 receptor by corticosterone may promote the malignant phenotype of glioblastoma.

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1	Gui H, Tong Q, Qu W, Mao CM and Dai SM: The endocannabinoid system and its therapeutic implications in rheumatoid arthritis. Int Immunopharmacol. 26:86–91. 2015. View Article : Google Scholar : PubMed/NCBI
2	Kano M, Ohno-Shosaku T, Hashimotodani Y, Uchigashima M and Watanabe M: Endocannabinoid-mediated control of synaptic transmission. Physiol Rev. 89:309–380. 2009. View Article : Google Scholar : PubMed/NCBI
3	Ligresti A, De Petrocellis L and Di Marzo V: From phytocannabinoids to cannabinoid receptors and endocannabinoids: Pleiotropic physiological and pathological roles through complex pharmacology. Physiol Rev. 96:1593–1659. 2016. View Article : Google Scholar : PubMed/NCBI
4	Cabral GA and Griffin-Thomas L: Cannabinoids as therapeutic agents for ablating neuroinflammatory disease. Endocr Metab Immune Disord Drug Targets. 8:159–172. 2008. View Article : Google Scholar : PubMed/NCBI
5	Sugimoto N, Ishibashi H, Nakamura H, Yachie A and Ohno-Shosaku T: Hypoxia-induced inhibition of the endocannabinoid system in glioblastoma cells. Oncol Rep. 38:3702–3708. 2017.PubMed/NCBI
6	Joëls M: Corticosteroids and the brain. J Endocrinol. 238:R121–R130. 2018. View Article : Google Scholar : PubMed/NCBI
7	Brattsand R and Linden M: Cytokine modulation by glucocorticoids: Mechanisms and actions in cellular studies. Aliment Pharmacol Ther. 10 (Suppl 2):S81–S92. 1996. View Article : Google Scholar
8	Wamsteeker JI, Kuzmiski JB and Bains JS: Repeated stress impairs endocannabinoid signaling in the paraventricular nucleus of the hypothalamus. J Neurosci. 30:11188–11196. 2010. View Article : Google Scholar : PubMed/NCBI
9	Leu H, Sugimoto N, Shimizu M, Toma T, Wada T, Ohta K and Yachie A: Tumor necrosis factor-α modifies the effects of Shiga toxin on glial cells. Int Immunopharmacol. 38:139–143. 2016. View Article : Google Scholar : PubMed/NCBI
10	Sugimoto N, Miwa S, Nakamura H, Tsuchiya H and Yachie A: Protein kinase A and Epac activation by cAMP regulates the expression of glial fibrillary acidic protein in glial cells. Arch Biol Sci. 68:795–801. 2016. View Article : Google Scholar
11	Solinas G and Becattini B: JNK at the crossroad of obesity, insulin resistance, and cell stress response. Mol Metab. 6:174–184. 2016. View Article : Google Scholar : PubMed/NCBI
12	Ortega A, Rangel-López E, Hidalgo-Miranda A, Morales A, Ruiz-García E, Meneses-García A, Herrera-Gómez A, Aguilar-Ponce JL, González-Herrera IG, Guevara-Salazar P, et al: On the effects of CP 55–940 and other cannabinoid receptor agonists in C6 and U373 cell lines. Toxicol In Vitro. 29:1941–1951. 2015. View Article : Google Scholar : PubMed/NCBI
13	Moreno-Smith M, Lutgendorf SK and Sood AK: Impact of stress on cancer metastasis. Future Oncol. 6:1863–1881. 2010. View Article : Google Scholar : PubMed/NCBI
14	Guindon J and Hohmann AG: The endocannabinoid system and cancer: Therapeutic implication. Br J Pharmacol. 163:1447–1463. 2011. View Article : Google Scholar : PubMed/NCBI
15	Klein TW: Cannabinoid-based drugs as anti-inflammatory therapeutics. Nat Rev Immunol. 5:400–411. 2005. View Article : Google Scholar : PubMed/NCBI
16	Echigo R, Sugimoto N, Yachie A and Ohno-Shosaku T: Cannabinoids inhibit peptidoglycan-induced phosphorylation of NF-κB and cell growth in U87MG human malignant glioma cells. Oncol Rep. 28:1176–1180. 2012. View Article : Google Scholar : PubMed/NCBI
17	Gurley SN, Abidi AH, Allison P, Guan P, Duntsch C, Robertson JH, Kosanke SD, Keir ST, Bigner DD, Elberger AJ and Moore BM II: Mechanism of anti-glioma activity and in vivo efficacy of the cannabinoid ligand KM-233. J Neurooncol. 110:163–177. 2012. View Article : Google Scholar : PubMed/NCBI
18	Guzmán M: Cannabinoids: Potential anticancer agents. Nat Rev Cancer. 3:745–755. 2003. View Article : Google Scholar : PubMed/NCBI
19	Salazar M, Carracedo A, Salanueva IJ, Hernández-Tiedra S, Lorente M, Egia A, Vázquez P, Blázquez C, Torres S, García S, et al: Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells. J Clin Invest. 119:1359–1372. 2009. View Article : Google Scholar : PubMed/NCBI
20	Sarfaraz S, Adhami VM, Syed DN, Afaq F and Mukhtar H: Cannabinoids for cancer treatment: Progress and promise. Cancer Res. 68:339–342. 2008. View Article : Google Scholar : PubMed/NCBI
21	Jang BC, Lim KJ, Suh MH, Park JG and Suh SI: Dexamethasone suppresses interleukin-1beta-induced human beta-defensin 2 mRNA expression: involvement of p38 MAPK, JNK, MKP-1, and NF-kappaB transcriptional factor in A549 cells. FEMS Immunol Med Microbiol. 51:171–184. 2007. View Article : Google Scholar : PubMed/NCBI
22	Chantong B, Kratschmar DV, Nashev LG, Balazs Z and Odermatt A: Mineralocorticoid and glucocorticoid receptors differentially regulate NF-kappaB activity and pro-inflammatory cytokine production in murine BV-2 microglial cells. J Neuroinflammation. 9:2602012. View Article : Google Scholar : PubMed/NCBI
23	Huang SS, Chen DZ, Wu H, Chen RC, Du SJ, Dong JJ, Liang G, Xu LM, Wang XD, Yang YP, et al: Cannabinoid receptors are involved in the protective effect of a novel curcumin derivative C66 against CCl4-induced liver fibrosis. Eur J Pharmacol. 779:22–30. 2016. View Article : Google Scholar : PubMed/NCBI
24	Nakatani Y, Amano T and Takeda H: Corticosterone inhibits the proliferation of C6 glioma cells via the translocation of unphosphorylated glucocorticoid receptor. Biol Pharm Bull. 39:1121–1129. 2016. View Article : Google Scholar : PubMed/NCBI
25	Zoerner AA, Gutzki FM, Batkai S, May M, Rakers C, Engeli S, Jordan J and Tsikas D: Quantification of endocannabinoids in biological systems by chromatography and mass spectrometry: A comprehensive review from an analytical and biological perspective. Biochim Biophys Acta. 1811:706–723. 2011. View Article : Google Scholar : PubMed/NCBI