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Anti-Cancer Agents in Medicinal Chemistry

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ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

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General Research Article

Apoptotic Effects of N-(2-Hydroxyphenyl)-2-Propylpentanamide on U87-MG and U-2 OS Cells and Antiangiogenic Properties

Author(s): Paola Castillo-Juárez, Sebastián C. Sanchez, Alma D. Chávez-Blanco, Humberto L. Mendoza-Figueroa and José Correa-Basurto*

Volume 21, Issue 11, 2021

Published on: 28 July, 2020

Page: [1451 - 1459] Pages: 9

DOI: 10.2174/1871520620666200728125356

Price: $65

Abstract

Background and Objective: Histone Deacetylases (HDACs) are important therapeutic targets for many types of human cancers. A derivative of valproic acid, N-(2-hydroxyphenyl)-2-propylpentanamide (HOAAVPA), has antiproliferative properties on some cancer cell lines and inhibits the HDAC1 isoform.

Materials and Methods: In this work, HO-AAVPA was tested as an antiproliferative agent in U87-MG (human glioblastoma) and U-2 OS cells (human osteosarcoma), which are types of cancer that are difficult to treat, and its antiangiogenic properties were explored.

Results: HO-AAVPA had antiproliferative effects at 48h with an IC50=0.655mM in U87-MG cells and an IC50=0.453mM in U-2 OS cells. Additionally, in the colony formation assay, HO-AAVPA decreased the number of colonies by approximately 99% in both cell lines and induced apoptosis by 31.3% in the U-2 OS cell line and by 78.2% in the U87-MG cell line. Additionally, HO-AAVPA reduced the number of vessels in Chorioallantoic Membranes (CAMs) by approximately 67.74% and IL-6 levels in both cell lines suggesting that the biochemical mechanism on cancer cell of HO-AAVPA is different compared to VPA.

Conclusion: HO-AAVPA has antiproliferative effects on glioblastoma and osteosarcoma and antiangiogenic properties.

Keywords: Antiproliferative, proapoptotic, HO-AAVPA, antiangiogenic properties, U87-MG, U-2 OS.

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[1]
Maleszewska, M.; Wojtas, B.; Kamińska, B. Deregulation of epigenetic mechanisms in cancer. Postepy Biochem., 2018, 64(2), 148-156.
[http://dx.doi.org/10.18388/pb.2018_125] [PMID: 30656897]
[2]
Mai, A.; Massa, S.; Rotili, D.; Cerbara, I.; Valente, S.; Pezzi, R.; Simeoni, S.; Ragno, R. Histone deacetylation in epigenetics: an attractive target for anticancer therapy. Med. Res. Rev., 2005, 25(3), 261-309.
[http://dx.doi.org/10.1002/med.20024] [PMID: 15717297]
[3]
Palmieri, C.; Coombes, R.C.; Vigushin, D.M. Targeted histone deacetylase inhibition for cancer prevention and therapy. Prog. Drug Res., 2005, 63, 147-181.
[http://dx.doi.org/10.1007/3-7643-7414-4_7] [PMID: 16265880]
[4]
Seto, E.; Yoshida, M. Erasers of histone acetylation: The histone deacetylase enzymes. Cold Spring Harb. Perspect. Biol., 2014, 6(4), a018713.
[http://dx.doi.org/10.1101/cshperspect.a018713] [PMID: 24691964]
[5]
Yang, H.; Salz, T.; Zajac-Kaye, M.; Liao, D.; Huang, S.; Qiu, Y. Overexpression of histone deacetylases in cancer cells is controlled by interplay of transcription factors and epigenetic modulators. FASEB J., 2014, 28(10), 4265-4279.
[http://dx.doi.org/10.1096/fj.14-250654] [PMID: 24948597]
[6]
Santini, V.; Gozzini, A.; Ferrari, G. Histone deacetylase inhibitors: Molecular and biological activity as a premise to clinical application. Curr. Drug Metab., 2007, 8(4), 383-393.
[http://dx.doi.org/10.2174/138920007780655397] [PMID: 17504226]
[7]
Ellis, L.; Hammers, H.; Pili, R. Targeting tumor angiogenesis with histone deacetylase inhibitors. Cancer Lett., 2009, 280(2), 145-153.
[http://dx.doi.org/10.1016/j.canlet.2008.11.012] [PMID: 19111391]
[8]
Noureen, N.; Rashid, H.; Kalsoom, S. Identification of type-specific anticancer histone deacetylase inhibitors: Road to success. Cancer Chemother. Pharmacol., 2010, 66(4), 625-633.
[http://dx.doi.org/10.1007/s00280-010-1324-y] [PMID: 20401613]
[9]
Chen, H.P.; Zhao, Y.T.; Zhao, T.C. Histone deacetylases and mechanisms of regulation of gene expression. Crit. Rev. Oncog., 2015, 20(1-2), 35-47.
[http://dx.doi.org/10.1615/CritRevOncog.2015012997] [PMID: 25746103]
[10]
Liu, T.; Ma, W.; Xu, H.; Huang, M.; Zhang, D.; He, Z.; Zhang, L.; Brem, S.; O’Rourke, D.M.; Gong, Y.; Mou, Y.; Zhang, Z.; Fan, Y. PDGF-mediated mesenchymal transformation renders endothelial resistance to anti-VEGF treatment in glioblastoma. Nat. Commun., 2018, 9(1), 3439.
[http://dx.doi.org/10.1038/s41467-018-05982-z] [PMID: 30150753]
[11]
Rastogi, S.; Kumar, R.; Sankineani, S.R.; Marimuthu, K.; Rijal, L.; Prakash, S.; Jalan, D.; Khan, S.A.; Sharma, M.C. Role of vascular endothelial growth factor as a tumour marker in osteosarcoma: A prospective study. Int. Orthop., 2012, 36(11), 2315-2321.
[http://dx.doi.org/10.1007/s00264-012-1663-x] [PMID: 23015149]
[12]
Sawa, H.; Murakami, H.; Ohshima, Y.; Murakami, M.; Yamazaki, I.; Tamura, Y.; Mima, T.; Satone, A.; Ide, W.; Hashimoto, I.; Kamada, H. Histone deacetylase inhibitors such as sodium butyrate and trichostatin A inhibit Vascular Endothelial Growth Factor (VEGF) secretion from human glioblastoma cells. Brain Tumor Pathol., 2002, 19(2), 77-81.
[http://dx.doi.org/10.1007/BF02478931] [PMID: 12622137]
[13]
Krämer, O.H.; Zhu, P.; Ostendorff, H.P.; Golebiewski, M.; Tiefenbach, J.; Peters, M.A.; Brill, B.; Groner, B.; Bach, I.; Heinzel, T.; Göttlicher, M. The histone deacetylase inhibitor valproic acid selectively induces proteasomal degradation of HDAC2. EMBO J., 2003, 22(13), 3411-3420.
[http://dx.doi.org/10.1093/emboj/cdg315] [PMID: 12840003]
[14]
Gopaul, S.; Farrell, K.; Abbott, F. Effects of age and polytherapy, risk factors of Valproic Acid (VPA) hepatotoxicity, on the excretion of thiol conjugates of (E)-2,4-diene VPA in people with epilepsy taking VPA. Epilepsia, 2003, 44(3), 322-328.
[http://dx.doi.org/10.1046/j.1528-1157.2003.07202.x] [PMID: 12614387]
[15]
Luna-Palencia, G.; Martinez-Ramos, F.; Vasquez-Moctezuma, I.; Fragoso-Vazquez, M.; Mendieta-Wejebe, J.; Padilla-Martínez, I. Three amino acid derivatives of valproic acid: Design, synthesis, theoretical and experimental evaluation as anticancer agents. Anti-Cancer Agents Med. Chem., 2014, 14, 984-993.
[16]
Prestegui-Martel, B.; Bermúdez-Lugo, J.A.; Chávez-Blanco, A.; Dueñas-González, A.; García-Sánchez, J.R.; Pérez-González, O.A.; Padilla-Martínez, I.I.; Fragoso-Vázquez, M.J.; Mendieta-Wejebe, J.E.; Correa-Basurto, A.M.; Méndez-Luna, D.; Trujillo-Ferrara, J.; Correa-Basurto, J. N-(2-hydroxyphenyl)-2-propylpentanamide, a valproic acid aryl derivative designed in silico with improved antiproliferative activity in HeLa, rhabdomyosarcoma and breast cancer cells. J. Enzyme Inhib. Med. Chem., 2016, 31(sup3), 140-149.
[http://dx.doi.org/10.1080/14756366.2016.1210138] [PMID: 27483122]
[17]
Correa-Basurto, A.M.; Romero-Castro, A.; Correa-Basurto, J.; Hernández-Rodríguez, M.; Soriano-Ursúa, M.A.; García-Machorro, J.; Tolentino-López, L.E.; Rosales-Hernández, M.C.; Mendieta-Wejebe, J.E. Pharmacokinetics and tissue distribution of N-(2-hydroxyphenyl)-2-propylpentanamide in Wistar Rats and its binding properties to human serum albumin. J. Pharm. Biomed. Anal., 2019, 162, 130-139.
[http://dx.doi.org/10.1016/j.jpba.2018.09.010] [PMID: 30236821]
[18]
von Hoff, D.D. Human tumor cloning assays: applications in clinical oncology and new antineoplastic agent development. Cancer Metastasis Rev., 1988, 7(4), 357-371.
[http://dx.doi.org/10.1007/BF00051376] [PMID: 3061679]
[19]
Katayama, Y.; Uchino, J.; Chihara, Y.; Tamiya, N.; Kaneko, Y.; Yamada, T.; Takayama, K. Tumor neovascularization and developments in therapeutics. Cancers (Basel), 2019, 11(3), E316.
[http://dx.doi.org/10.3390/cancers11030316] [PMID: 30845711]
[20]
Costache, M.I.; Ioana, M.; Iordache, S.; Ene, D.; Costache, C.A.; Săftoiu, A. VEGF expression in pancreatic cancer and other malignancies: A review of the literature. Rom. J. Intern. Med., 2015, 53(3), 199-208.
[http://dx.doi.org/10.1515/rjim-2015-0027] [PMID: 26710495]
[21]
Coussens, L.M.; Werb, Z.; Coussens, L.M.; Werb, Z. Inflammation and cancer. Nature, 2002, 420(6917), 860-867.
[http://dx.doi.org/10.1038/nature01322] [PMID: 12490959]
[22]
Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: The next generation. Cell, 2011, 144(5), 646-674.
[http://dx.doi.org/10.1016/j.cell.2011.02.013] [PMID: 21376230]
[23]
Farooq, M.; El-Faham, A.; Khattab, S.N.; Elkayal, A.M.; Ibrahim, M.F.; Taha, N.A.; Baabbad, A.; Wadaan, M.A.; Hamed, E.A. Biological screening of novel derivatives of valproic acid for anticancer and antiangiogenic properties. Asian Pac. J. Cancer Prev., 2014, 15(18), 7785-7792.
[http://dx.doi.org/10.7314/APJCP.2014.15.18.7785] [PMID: 25292064]
[24]
Das, C.M.; Aguilera, D.; Vasquez, H.; Prasad, P.; Zhang, M.; Wolff, J.E.; Gopalakrishnan, V. Valproic acid induces p21 and topoisomerase-II (α/β) expression and synergistically enhances etoposide cytotoxicity in human glioblastoma cell lines. J. Neurooncol., 2007, 85(2), 159-170.
[http://dx.doi.org/10.1007/s11060-007-9402-7] [PMID: 17534580]
[25]
Contis-Montes de Oca, A.; Rodarte-Valle, E.; Rosales-Hernández, M.C.; Abarca-Rojano, E.; Rojas-Hernández, S.; Fragoso-Vázquez, M.J.; Mendieta-Wejebe, J.E.; Correa-Basurto, A.M.; Vázquez-Moctezuma, I.; Correa-Basurto, J. N-(2′-Hydroxyphenyl)-2-propylpentanamide (OH-VPA), a histone deacetylase inhibitor, induces the release of nuclear HMGB1 and modifies ROS levels in HeLa cells. Oncotarget, 2018, 9(70), 33368-33381.
[http://dx.doi.org/10.18632/oncotarget.26077] [PMID: 30279967]
[26]
Gopinathan, G.; Milagre, C.; Pearce, O.M.T.; Reynolds, L.E.; Hodivala-Dilke, K.; Leinster, D.A.; Zhong, H.; Hollingsworth, R.E.; Thompson, R.; Whiteford, J.R.; Balkwill, F. Interleukin-6 stimulates defective angiogenesis. Cancer Res., 2015, 75(15), 3098-3107.
[http://dx.doi.org/10.1158/0008-5472.CAN-15-1227] [PMID: 26081809]
[27]
Sixto-López, Y.; Bello, M.; Correa-Basurto, J. Exploring the inhibitory activity of valproic acid against the HDAC family using an MMGBSA approach. J. Comput. Aided Mol. Des., 2020, 34(8), 857-878.
[http://dx.doi.org/10.1007/s10822-020-00304-2] [PMID: 32180123]
[28]
Gatla, H.R.; Muniraj, N.; Thevkar, P.; Yavvari, S.; Sukhavasi, S.; Makena, M.R. Regulation of chemokines and cytokines by histone deacetylases and an update on histone decetylase inhibitors in human diseases. Int. J. Mol. Sci., 2019, 20(5), E1110.
[http://dx.doi.org/10.3390/ijms20051110] [PMID: 30841513]
[29]
Mantovani, A.; Barajon, I.; Garlanda, C. Europe PMC Funders Group. IL-1 and IL-1 regulatory pathways in cancer progression and therapy. Immunol. Rev., 2018, 281(1), 57-61.
[30]
Fisher, D.T.; Appenheimer, M.M.; Evans, S.S. The two faces of IL-6 in the tumor microenvironment. Semin. Immunol., 2014, 26(1), 38-47.
[http://dx.doi.org/10.1016/j.smim.2014.01.008] [PMID: 24602448]

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