Isatin Inhibits SH-SY5Y Neuroblastoma Cell Invasion and Metastasis through LSD1 Activity Inhibition

Isatin Inhibits SH-SY5Y Neuroblastoma Cell Invasion and Metastasis through LSD1 Activity Inhibition

Loading document ...
Page
of
Loading page ...

Author(s)

Author(s): Shaobo Cong, Lin Hou, Haoyue Luo, Yanan Hua, Xue Li, Fangling Wang, Li Zhang, Zheng Zhang, Ning Li

Download Full PDF Read Complete Article

DOI: 10.18483/ijSci.1986 12 17 27-32 Volume 8 - Apr 2019

Abstract

Isatin has received much attention in recent years due to its anti-cancer properties[1], which offer important medical benefits. Isatin is an endogenous oxidized indole with a wide spectrum of behavioral and metabolic effects[2] and is commonly found in mammalian tissues and fluids[3]. It has many possible uses on the biomedical field[4] [5]and has also been investigated as a potential anti-cancer drug. However, its effects on neuroblastoma (NB) cells is still a mystery. This research aimed to elucidate the effects of Isatin on neuroblastoma cells metastasis and invasion and the underlying mechanism. Neuroblastoma cells viability was tested by CCK8. NB cells invasion and migration ability were tested by transwell and wound healing experiment. The mRNA relative expression of related molecules are detected by Rt-PCR and q-PCR. The protein relative expression of related molecules are detected by Simple western blotting. Our results demonstrated that isatin could inhibit neuroblastoma cell proliferation, invasion, and migration in a dose-dependent manner. Moreover, isatin increases the expression level of H3K4m1, PTEN. All results support the potential anti-metastatic effect of isatin in neuroblastoma cells.

Keywords

Isatin, Neuroblastoma, PTEN, LSD1, Invasion

References

  1. Vine KL, Matesic L, Locke JM, Ranson M and Skropeta D. Cytotoxic and Anticancer Activities of Isatin and Its Derivatives: A Comprehensive Review from 2000-2008. Anti-Cancer Agents in Medicinal Chemistry 2009; 9: 397-414.
  2. Medvedev A, Buneeva O and Glover V. Biological targets for isatin and its analogues: Implications for therapy. Biologics : targets & therapy 2007; 1: 151-162.
  3. Medvedev AE, Clow A, Sandler M and Glover V. Isatin: a link between natriuretic peptides and monoamines? Biochem Pharmacol 1996; 52: 385-391.
  4. da Silva JFM, Garden SJ and Pinto AC. The chemistry of isatins: a review from 1975 to 1999. Journal of the Brazilian Chemical Society 2001; 12: 273-324.
  5. Edmondson DE, Mattevi A, Binda C, Li M and Hubalek F. Structure and mechanism of monoamine oxidase. Current Medicinal Chemistry 2004; 11: 1983-1993.
  6. Maris JM. Recent Advances in Neuroblastoma. New England Journal of Medicine 2010; 362: 2202-2211.
  7. Adamo A, Sese B, Boue S, Castano J, Paramonov I, Barrero MJ and Belmonte JCI. LSD1 regulates the balance between self-renewal and differentiation in human embryonic stem cells. Nature Cell Biology 2011; 13: 652-U265.
  8. Brodeur GM, Pritchard J, Berthold F, Carlsen NLT, Castel V, Castleberry RP, Debernardi B, Evans AE, Favrot M, Hedborg F, Kaneko M, Kemshead J, Lampert F, Lee REJ, Look AT, Pearson ADJ, Philip T, Roald B, Sawada T, Seeger RC, Tsuchida Y and Voute PA. REVISIONS OF THE INTERNATIONAL CRITERIA FOR NEUROBLASTOMA DIAGNOSIS, STAGING, AND RESPONSE TO TREATMENT. Journal of Clinical Oncology 1993; 11: 1466-1477.
  9. Maris JM, Hogarty MD, Bagatell R and Cohn SL. Neuroblastoma. The Lancet 2007; 369: 2106-2120.
  10. Song J, Hou L, Ju C, Zhang J, Ge Y and Yue W. Isatin inhibits proliferation and induces apoptosis of SH-SY5Y neuroblastoma cells in vitro and in vivo. Eur J Pharmacol 2013; 702: 235-241.
  11. Fitzgerald JC, Ufer C and Billett EE. A link between monoamine oxidase-A and apoptosis in serum deprived human SH-SY5Y neuroblastoma cells. J Neural Transm (Vienna) 2007; 114: 807-810.
  12. Chen Y, Yang YT, Wang F, Wan K, Yarnane K, Zhang Y and Lei M. Crystal structure of human histone lysine-specific demethylase 1 (LSD1). Proceedings of the National Academy of Sciences of the United States of America 2006; 103: 13956-13961.
  13. Shi Y, Lan F, Matson C, Mulligan P, Whetstine JR, Cole PA, Casero RA and Shi Y. Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell 2004; 119: 941-953.
  14. Escriva M, Peiro S, Herranz N, Villagrasa P, Dave N, Montserrat-Sentis B, Murray SA, Franci C, Gridley T, Virtanen I and Garcia de Herreros A. Repression of PTEN phosphatase by Snail1 transcriptional factor during gamma radiation-induced apoptosis. Mol Cell Biol 2008; 28: 1528-1540.
  15. Lin Y, Wu Y, Li J, Dong C, Ye X, Chi YI, Evers BM and Zhou BP. The SNAG domain of Snail1 functions as a molecular hook for recruiting lysine-specific demethylase 1. EMBO J 2010; 29: 1803-1816.
  16. Shao G-B, Huang X-J, Gong A-H, Zhang Z-J, Lu R-Z and Sang J-R. Histone demethylase LSD1 and its biological functions. Hereditas (Beijing) 2010; 32: 331-338.
  17. Lim S, Janzer A, Becker A, Zimmer A, Schule R, Buettner R and Kirfel J. Lysine-specific demethylase 1 (LSD1) is highly expressed in ER-negative breast cancers and a biomarker predicting aggressive biology. Carcinogenesis 2010; 31: 512-520.
  18. Schulte JH, Lim S, Schramm A, Friedrichs N, Koster J, Versteeg R, Ora I, Pajtler K, Klein-Hitpass L, Kuhfittig-Kulle S, Metzger E, Schule R, Eggert A, Buettner R and Kirfel J. Lysine-specific demethylase 1 is strongly expressed in poorly differentiated neuroblastoma: implications for therapy. Cancer Res 2009; 69: 2065-2071.
  19. Lin Y, Kang T and Zhou BP. Doxorubicin enhances Snail/LSD1-mediated PTEN suppression in a PARP1-dependent manner. Cell Cycle 2014; 13: 1708-1716.
  20. Araki KMYaM. Tumor suppressor PTEN: modulator of cell signaling,
  21. growth, migration and apoptosis. Journal of Cell Science 2001; 114: 2375-2382
  22. Yokoyama A, Baba T, RI, KI, JK, YO, TS, Kiyoshi Takagi, K-iM, MO, aAS and YS. IdentificationofMyelinTranscriptionFactor1(MyT1)asa SubunitoftheNeuralCellType-specificLysine-specific Demethylase1(LSD1)Complex. THE JOURNAL OF BIOLOGICAL CHEMISTRY 2014; 289: 18152–18162.
  23. Stambolic V. Negative Regulation of PKB/Akt-Dependent
  24. Cell Survival by the Tumor Suppressor PTEN. cell 1998;
  25. Nan. PTEN inhibits the migration and invasion of HepG2 cells by coordinately decreasing MMP expression via the PI3K/Akt pathway. Oncology Reports 2010; 23:
  26. Tamura M, Gu JG, Matsumoto K, Aota S, Parsons R and Yamada KM. Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN. Science 1998; 280: 1614-1617.
  27. Yamada KM and Araki M. Tumor suppressor PTEN: modulator of cell signaling, growth, migration and apoptosis. Journal of Cell Science 2001; 114: 2375-2382.
  28. Igosheva N, Lorz C, O'Conner E, Glover V and Mehmet H. Isatin, an endogenous monoamine oxidase inhibitor, triggers a dose- and time-dependent switch from apoptosis to necrosis in human neuroblastoma cells. Neurochem Int 2005; 47: 216-224.
  29. Xu PP, Hou L, Ju CX, Zhang Z, Sun WY, Zhang L, Song JL, Lv YQ, Liu L, Chen ZX and Wang YH. Isatin inhibits the proliferation and invasion of SH-SY5Y neuroblastoma cells. Molecular Medicine Reports 2016; 13: 2757-2762.
  30. Sun W, Zhang L, Hou L, Ju C, Zhao S and Wei Y. Isatin inhibits SH-SY5Y neuroblastoma cell invasion and metastasis through MAO/HIF-1alpha/CXCR4 signaling. Anticancer Drugs 2017; 28: 645-653.
  31. Justo LA, Duran R, Alfonso M, Fajardo D and Faro LRF. Effects and mechanism of action of isatin, a MAO inhibitor, on in vivo striatal dopamine release. Neurochemistry International 2016; 99: 147-157.
  32. Chen C, Wang Y, Wang S, Liu Y, Zhang J, Xu Y, Zhang Z, Bao W and Wu S. LSD1 sustains estrogen-driven endometrial carcinoma cell proliferation through the PI3K/AKT pathway via di-demethylating H3K9 of cyclin D1. Int J Oncol 2017; 50: 942-952.
  33. Zhong H, Chiles K, Feldser D, Laughner E, Hanrahan C, Georgescu MM, Simons JW and Semenza GL. Modulation of hypoxia-inducible factor 1 alpha expression by the epidermal growth factor/phosphatidylinositol 3-kinase/PTEN/AKT/FRAP pathway in human prostate cancer cells: Implications for tumor angiogenesis and therapeutics. Cancer Research 2000; 60: 1541-1545.
  34. Berns K, Horlings HM, Hennessy BT, Madiredjo M, Hijmans EM, Beelen K, Linn SC, Gonzalez-Angulo AM, Stemke-Hale K, Hauptmann M, Beijersbergen RL, Mills GB, de Vijver MJV and Bernards R. A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer. Cancer Cell 2007; 12: 395-402.
  35. Havrylyuk D, Zimenkovsky B, Vasylenko O, Gzella A and Lesyk R. Synthesis of New 4-Thiazolidinone-, Pyrazoline-, and Isatin-Based Conjugates with Promising Antitumor Activity. Journal of Medicinal Chemistry 2012; 55: 8630-8641.

Cite this Article:

  • BibTex
  • RIS
  • APA
  • Harvard
  • IEEE
  • MLA
  • Vancouver
  • Chicago

International Journal of Sciences is Open Access Journal.
This article is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) License.
Author(s) retain the copyrights of this article, though, publication rights are with Alkhaer Publications.

Search Articles

Issue March 2019

Volume 8, March 2019


Table of Contents


Order Print Copy

World-wide Delivery is FREE

Share this Issue with Friends:


Submit your Paper