The Anticancer Action of a Novel 1,2,4-Triazine Sulfonamide Derivative in Colon Cancer Cells
Abstract
:1. Introduction
2. Results
2.1. Chemistry
2.2. Biological Studies
3. Discussion
4. Materials and Methods
4.1. MM131 Synthesis
4.1.1. General
4.1.2. Synthesis of N-(R)-(1-hydroxypropan-2-yl)-4-(3-methyl-5-methylsulfonyl-1H-pyrazolo[4,3-e][1,2,4]triazyn-1-yl)benzenesulfonamide (2)
4.1.3. Synthesis of Tricyclic Sulfonamides (MM131)
4.2. Cell Culture of HT-29 and DLD-1 Cells
4.3. Cell Viability Assay
4.4. [3H]-Thymidine Incorporation Assay
4.5. Flow Cytometry Assessment of Annexin V Binding
4.6. Acridine Orange/ethidium Bromide Fluorescent Staining
4.7. Analysis of Caspase-8 Enzymatic Activity
4.8. Caspase-9 Enzymatic Activity Assay
4.9. Caspase-3/7 Enzymatic Activity Assay
4.10. Cell Cycle Analysis
4.11. Determination of sICAM-1, mTOR, Cathepsin B, Beclin-1
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
Sample Availability
Abbreviations
13C-NMR | Carbon-13 Nuclear Magnetic Resonance |
1H-NMR | Hydrogen-1 Nuclear Magnetic Resonance |
anti-EGFR | anti-epidermal growth factor receptor therapy |
APAF1 | apoptotic protease activating factor 1 |
ATCC | American Type Culture Collection |
CK2 | ubiquitous serine/threonine protein kinase |
COX-2 | cyclooxygenase-2 |
CRC | colorectal cancer |
DLD-1 | colorectal cancer cell line |
DMSO | dimethyl sulfoxide |
EDTA | ethylenediamine tetraacetic acid |
EGFR | epidermal growth factor receptor |
ELISA | Enzyme Immunosorbent Assay |
ERK 1/2 | extracellular signal-regulated kinase 1/2 |
EtOH | Ethanol |
FADD | Fas-associated protein with death domain |
FDA | Food and Drug Administration |
FGFR | fibroblast growth factor receptor |
GSK-3β | glycogen synthase kinase 3 β |
H1299 | non-small cell lung carcinoma cell line |
HRP | horseradish peroxidase |
HT-29 | colorectal cancer cell line |
IAP | inhibitors of apoptosis proteins |
IC50 | half maximal inhibitory concentration |
JAK | janus-activated kinases |
MAPK | mitogen-activated protein kinase |
MDA-MB-435 | melanoma cancer cell line |
MeCN | acetonitrile |
MMP-2 | matrix metalloproteinase 2 |
MMP-9 | matrix metalloproteinase 9 |
mTOR | mechanistic target of rapamycin |
MTT | 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide |
NaN3 | Sodium azide |
PBS | Phosphate Buffered Saline |
PI | Propidium Iodide |
PI3K | phosphoinositide 3-kinase |
Pim-1 | proviral integration site for Moloney murine leukemia virus-1 kinase |
rt | room temperature |
SD | Standard Deviation |
SDS | Sodium Dodecyl Sulfate |
SEM | standard error of the mean |
sICAM-1 | soluble intercellular adhesion molecule-1 |
SYK | spleen tyrosine kinase |
T-47D | breast cancer cell line |
TCA | Trichloroacetic acid |
Tie-2 | tyrosine kinase with immunoglobulin and epidermal growth factorhomology domains-2 |
TLC | thin layer chromatography |
TMB | Tetramethylbenzidine |
TMS | tetramethylsilane |
TNF | tumor necrosis factor |
TRAIL | tumor necrosis factor (TNF)-related apoptosis-inducing ligand |
VEGF | vascular endothelial growth factor |
VEGFR | vascular endothelial growth factor receptor |
References
- Favoriti, P.; Carbone, G.; Greco, M.; Pirozzi, F.; Pirozzi, R.E.M.; Corcione, F. Worldwide burden of colorectal cancer: A review. Updat. Surg. 2016, 68, 7–11. [Google Scholar] [CrossRef] [PubMed]
- Dekker, E.; Tanis, P.J.; Vleugels, J.L.A.; Kasi, P.M.; Wallace, M.B. Colorectal cancer. Lancet 2019, 394, 1467–1480. [Google Scholar] [CrossRef]
- Kwong, T.N.; Wang, X.; Nakatsu, G.; Chow, T.C.; Tipoe, T.; Dai, R.Z.; Tsoi, K.K.; Wong, M.C.; Tse, G.; Chan, M.T.; et al. Association Between Bacteremia From Specific Microbes and Subsequent Diagnosis of Colorectal Cancer. Gastroenterology 2018, 155, 383–390.e8. [Google Scholar] [CrossRef] [PubMed]
- Yothers, G.; O’Connell, M.J.; Allegra, C.J.; Kuebler, J.P.; Colangelo, L.H.; Petrelli, N.J.; Wolmark, N. Oxaliplatin As Adjuvant Therapy for Colon Cancer: Updated Results of NSABP C-07 Trial, Including Survival and Subset Analyses. J. Clin. Oncol. 2011, 29, 3768–3774. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hurwitz, H.; Fehrenbacher, L.; Novotny, W.; Cartwright, T.; Hainsworth, J.; Heim, W.; Berlin, J.; Baron, A.; Griffing, S.; Holmgren, E.; et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N. Engl. J Med. 2004, 350, 2335–2342. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Huijberts, S.C.; Van Geel, R.M.; Bernards, R.; Beijnen, J.H.; Steeghs, N. Encorafenib, binimetinib and cetuximab combined therapy for patients with BRAFV600E mutant metastatic colorectal cancer. Futur. Oncol. 2020, 16, 161–173. [Google Scholar] [CrossRef]
- Sun, Z.; Qiu, Z.; Ma, B.; Wang, Z. Encorafenib enhances TRAIL-induced apoptosis of colorectal cancer cells dependent on p53/PUMA signaling. Cytotechnology 2020, 73, 1–8. [Google Scholar] [CrossRef]
- Bouchain, G.; Delorme, D. Novel hydroxamate and anilide derivatives as potent histone deacetylase inhibitors: Synthesis and antiproliferative evaluation. Curr. Med. Chem. 2003, 10, 2359–2372. [Google Scholar] [CrossRef]
- Mojzych, M.; Dolashki, A.; Voelter, W. Synthesis of pyrazolo[4,3- e ][1,2,4]triazine sulfonamides, novel Sildenafil analogs with tyrosinase inhibitory activity. Bioorganic Med. Chem. 2014, 22, 6616–6624. [Google Scholar] [CrossRef]
- Cheng, X.-C.; Wang, Q.; Fang, H.; Xu, W.-F. Role of sulfonamide group in matrix metalloproteinase inhibitors. Curr. Med. Chem. 2008, 15, 368–373. [Google Scholar] [CrossRef]
- Lu, Y.; Chen, J.; Xiao, M.; Li, W.; Miller, D.D. An Overview of Tubulin Inhibitors That Interact with the Colchicine Binding Site. Pharm. Res. 2012, 29, 2943–2971. [Google Scholar] [CrossRef] [Green Version]
- Koyuncu, I.; Gonel, A.; Kocyigit, A.; Temiz, E.; Durgun, M.; Supuran, C.T. Selective inhibition of carbonic anhydrase-IX by sulphonamide derivatives induces pH and reactive oxygen species-mediated apoptosis in cervical cancer HeLa cells. J. Enzym. Inhib. Med. Chem. 2018, 33, 1137–1149. [Google Scholar] [CrossRef] [Green Version]
- Mboge, M.Y.; McKenna, R.; Frost, S.C.; Bentham Science Publisher Atta-ur-Rahman; Zaman, K. Advances in Anti-Cancer Drug Development Targeting Carbonic Anhydrase IX and XII. Top. Anti-Cancer Res. 2016, 5, 3–42. [Google Scholar] [CrossRef] [Green Version]
- Miyamoto, S.; Kakutani, S.; Sato, Y.; Hanashi, A.; Kinoshita, Y.; Ishikawa, A. Drug review: Pazopanib. Jpn. J. Clin. Oncol. 2018, 48, 503–513. [Google Scholar] [CrossRef] [PubMed]
- Gimsing, P. Belinostat: A new broad acting antineoplastic histone deacetylase inhibitor. Expert Opin. Investig. Drugs 2009, 18, 501–508. [Google Scholar] [CrossRef] [PubMed]
- Lee, H.-Z.; Kwitkowski, V.E.; Del Valle, P.L.; Ricci, M.S.; Saber, H.; Habtemariam, B.A.; Bullock, J.; Bloomquist, E.; Shen, Y.L.; Chen, X.-H.; et al. FDA Approval: Belinostat for the Treatment of Patients with Relapsed or Refractory Peripheral T-cell Lymphoma. Clin. Cancer Res. 2015, 21, 2666–2670. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Medina, T.; Amaria, M.N.; Jimeno, A. Dabrafenib in the treatment of advanced melanoma. Drugs Today 2013, 49, 377–385. [Google Scholar]
- Swaika, A.; Crozier, J.A.; Joseph, R.W. Vemurafenib: An evidence-based review of its clinical utility in the treatment of metastatic melanoma. Drug. Des. Devel. Ther. 2014, 8, 775–787. [Google Scholar] [CrossRef] [Green Version]
- Chen, J.; Jin, S.; Abraham, V.; Huang, X.; Liu, B.; Mitten, M.J.; Nimmer, P.; Lin, X.; Smith, M.L.; Shen, Y.; et al. The Bcl-2/Bcl-XL/Bcl-w Inhibitor, Navitoclax, Enhances the Activity of Chemotherapeutic Agents In Vitro and In Vivo. Mol. Cancer Ther. 2011, 10, 2340–2349. [Google Scholar] [CrossRef] [Green Version]
- Rudin, C.M.; Hann, C.L.; Garon, E.B.; De Oliveira, M.R.; Bonomi, P.D.; Camidge, D.R.; Chu, Q.; Giaccone, G.; Khaira, D.; Ramalingam, S.S.; et al. Phase II Study of Single-Agent Navitoclax (ABT-263) and Biomarker Correlates in Patients with Relapsed Small Cell Lung Cancer. Clin. Cancer Res. 2012, 18, 3163–3169. [Google Scholar] [CrossRef] [Green Version]
- Kipps, T.J.; Eradat, H.; Grosicki, S.; Catalano, J.; Cosolo, W.; Dyagil, I.S.; Yalamanchili, S.; Chai, A.; Sahasranaman, S.; Punnoose, E.; et al. A phase 2 study of the BH3 mimetic BCL2 inhibitor navitoclax (ABT-263) with or without rituximab, in previously untreated B-cell chronic lymphocytic leukemia. Leuk. Lymphoma 2015, 56, 2826–2833. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cascioferro, S.; Parrino, B.; Spanò, V.; Carbone, A.; Montalbano, A.; Barraja, P.; Diana, P.; Cirrincione, G. Synthesis and antitumor activities of 1,2,3-triazines and their benzo- and heterofused derivatives. Eur. J. Med. Chem. 2017, 142, 74–86. [Google Scholar] [CrossRef] [PubMed]
- Cascioferro, S.; Parrino, B.; Spanò, V.; Carbone, A.; Montalbano, A.; Barraja, P.; Diana, P.; Cirrincione, G. An overview on the recent developments of 1,2,4-triazine derivatives as anticancer compounds. Eur. J. Med. Chem. 2017, 142, 328–375. [Google Scholar] [CrossRef] [PubMed]
- Cascioferro, S.; Parrino, B.; Spanò, V.; Carbone, A.; Montalbano, A.; Barraja, P.; Diana, P.; Cirrincione, G. 1,3,5-Triazines: A promising scaffold for anticancer drugs development. Eur. J. Med. Chem. 2017, 142, 523–549. [Google Scholar] [CrossRef]
- Gornowicz, A.; Szymanowska, A.; Mojzych, M.; Bielawski, K.; Bielawska, A. The Effect of Novel 7-methyl-5-phenyl-pyrazolo[4,3-e]tetrazolo[4,5-b][1,2,4]triazine Sulfonamide Derivatives on Apoptosis and Autophagy in DLD-1 and HT-29 Colon Cancer Cells. Int. J. Mol. Sci. 2020, 21, 5221. [Google Scholar] [CrossRef] [PubMed]
- Hermanowicz, J.M.; Szymanowska, A.; Sieklucka, B.; Czarnomysy, R.; Pawlak, K.; Bielawska, A.; Bielawski, K.; Kalafut, J.; Przybyszewska, A.; Surażyński, A.; et al. Exploration of novel heterofused 1,2,4-triazine derivative in colorectal cancer. J. Enzyme Inhib. 2021, 36, 535–548. [Google Scholar] [CrossRef] [PubMed]
- Rykowski, A.; Mojzych, M.; Karczmarzyk, Z. A New Synthesis of Pyrazolo- [4,3-e][1,2,4]triazines via Acid Promoted Ring Closure of the Phenylhydrazones of 5-Acyl-1,2,4-triazines. Heterocycles 2000, 53, 2175. [Google Scholar] [CrossRef]
- Rykowski, A.; Mojzych, M. Synthesis of Functionalized 1H-Pyrazolo[4,3-e][1,2,4]triazines and Their Fused Derivatives via Ipso-Substitution of Methylsulfonyl Group with O-, N-, S- and C-Nucleophiles. Heterocycles 2004, 63, 1829. [Google Scholar] [CrossRef]
- Mojzych, M.; Rykowski, A. Transformations of phenylhydrazones of 5-acyl-1,2,4-triazines to pyrazolo[4,3-e][1,2,4]triazines or 4-cyanopyrazole. J. Heterocycl. Chem. 2007, 44, 1003–1007. [Google Scholar] [CrossRef]
- Mojzych, M.; Ceruso, M.; Bielawska, A.; Bielawski, K.; Fornal, E.; Supuran, C.T. New pyrazolo[4,3 e][1,2,4]triazine sulfona-mides as carbonic anhydrase inhibitors. Bioorg. Med. Chem. 2015, 23, 3674–3680. [Google Scholar] [CrossRef] [PubMed]
- Bernat, Z.; Szymanowska, A.; Kciuk, M.; Kotwica-Mojzych, K.; Mojzych, M. Review of the Synthesis and Anticancer Properties of Pyrazolo[4,3-e][1,2,4]triazine Derivatives. Molecules 2020, 25, 3948. [Google Scholar] [CrossRef]
- Koehler, B.C.; Jäger, D.; Schulze-Bergkamen, H. Targeting cell death signaling in colorectal cancer: Current strategies and future perspectives. World J Gastroenterol. 2014, 28, 1923–1934. [Google Scholar] [CrossRef]
- Sale, M.J.; Cook, S.J. The BH3 mimetic ABT-263 synergizes with the MEK1/2 inhibitor selumetinib/AZD6244 to promote BIM-dependent tumour cell death and inhibit acquired resistance. Biochem. J. 2013, 450, 285–294. [Google Scholar] [CrossRef]
- Shima, H.; Tsurita, G.; Wada, S.; Hirohashi, Y.; Yasui, H.; Hayashi, H.; Miyakoshi, T.; Watanabe, K.; Murai, A.; Asanuma, H.; et al. Randomized phase II trial of survivin 2B peptide vaccination for patients with HLA -A24-positive pancreatic adenocarcinoma. Cancer Sci. 2019, 110, 2378–2385. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hua, H.; Kong, Q.; Zhang, H.; Wang, J.; Luo, T.; Jiang, Y. Targeting mTOR for cancer therapy. J. Hematol. Oncol. 2019, 12, 1–19. [Google Scholar] [CrossRef]
- Tian, T.; Li, X.; Zhang, J. mTOR Signaling in cancer and mTOR inhibitors in solid tumor targeting therapy. Int. J. Mol. Sci. 2019, 20, 755. [Google Scholar] [CrossRef] [Green Version]
- Pópulo, H.; Lopes, J.M.; Soares, P. The mTOR Signalling Pathway in Human Cancer. Int. J. Mol. Sci. 2012, 13, 1886–1918. [Google Scholar] [CrossRef]
- Schellerer, V.S.; Langheinrich, M.C.; Zver, V.; Grützmann, R.; Stürzl, M.; Gefeller, O.; Naschberger, E.; Merkel, S. Soluble intercellular adhesion molecule-1 is a prognostic marker in colorectal carcinoma. Int. J. Color. Dis. 2019, 34, 309–317. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Won, K.Y.; Kim, G.Y.; Lim, S.-J.; Kim, Y.W. Decreased Beclin-1 expression is correlated with the growth of the primary tumor in patients with squamous cell carcinoma and adenocarcinoma of the lung. Hum. Pathol. 2012, 43, 62–68. [Google Scholar] [CrossRef] [PubMed]
- Zhang, M.; Wang, L.; Zhao, S.; Guo, X.; Xu, Y.; Zheng, Z.; Lu, H.; Zheng, H. Effects of Beclin 1 overexpression on aggressive phenotypes of colon cancer cells. Oncol. Lett. 2018, 17, 2441–2450. [Google Scholar] [CrossRef]
- Sinha, A.A.; Gleason, D.F.; DeLeon, O.F.; Wilson, M.J.; Sloane, B.F. Localization of a biotinylated cathepsin B oligonucleotide probe in human prostate including invasive cells and invasive edges by in situ hybridization. Anat. Rec. Adv. Integr. Anat. Evol. Biol. 1993, 235, 233–240. [Google Scholar] [CrossRef] [PubMed]
- A Rempel, S.; Rosenblum, M.L.; Mikkelsen, T.; Yan, P.S.; Ellis, K.D.; A Golembieski, W.; Sameni, M.; Rozhin, J.; Ziegler, G.; Sloane, B.F. Cathepsin B expression and localization in glioma progression and invasion. Cancer Res. 1994, 54, 6027–6031. [Google Scholar]
- Matarrese, P.; Ascione, B.; Ciarlo, L.; Vona, R.; Leonetti, C.; Scarsella, M.; Mileo, A.M.; Catricalà, C.; Paggi, M.G.; Malorni, W. Cathepsin B inhibition interferes with metastatic potential of human melanoma: An in vitro and in vivo study. Mol. Cancer 2010, 9, 207. [Google Scholar] [CrossRef] [Green Version]
- Sevenich, L.; Schurigt, U.; Sachse, K.; Gajda, M.; Werner, F.; Müller, S.; Vasiljeva, O.; Schwinde, A.; Klemm, N.; Deussing, J.; et al. Synergistic antitumor effects of combined cathepsin B and cathepsin Z deficiencies on breast cancer progression and metastasis in mice. Proc. Natl. Acad. Sci. USA 2010, 107, 2497–2502. [Google Scholar] [CrossRef] [Green Version]
- Sevenich, L.; Werner, F.W.; Gajda, M.; Schurigt, U.; Sieber, C.; Muller, S.C.; Follo, M.Y.; Peters, C.; Reinheckel, T. Transgenic expression of human cathepsin B promotes progression and metastasis of polyoma-middle-T-induced breast cancer in mice. Oncogene 2010, 30, 54–64. [Google Scholar] [CrossRef] [Green Version]
- Campo, E.; Muñoz, J.; Miquel, R.; Palacín, A.; Cardesa, A.; Sloane, B.F.; Emmert-Buck, M.R. Cathepsin B expression in colorectal carcinomas correlates with tumor progression and shortened patient survival. Am. J. Pathol. 1994, 145, 301–309. [Google Scholar]
- Ruan, H.; Hao, S.; Young, P.; Zhang, H. Targeting Cathepsin B for Cancer Therapies. Horizons Cancer Res. 2015, 56, 23–40. [Google Scholar]
- Gornowicz, A.; Szymanowski, W.; Bielawska, A.; Szymanowska, A.; Czarnomysy, R.; Kałuża, Z.; Bielawski, K. Monoclonal anti-MUC1 antibody with novel octahydropyrazino[2,1-a:5,4-a’]diisoquinoline derivative as a potential multi-targeted strategy in MCF-7 breast cancer cells. Oncol. Rep. 2019, 42, 1391–1403. [Google Scholar] [CrossRef] [PubMed]
- Pawłowska, N.; Gornowicz, A.; Bielawska, A.; Surażyński, A.; Szymanowska, A.; Czarnomysy, R.; Bielawski, K. The molecular mechanism of anticancer action of novel octahydropyrazino[2,1-a:5,4-a’]diisoquinoline derivatives in human gastric cancer cells. Investig. New Drugs. 2018, 36, 970–984. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lepiarczyk, M.; Kałuża, Z.; Bielawska, A.; Czarnomysy, R.; Gornowicz, A.; Bielawski, K. Cytotoxic Activity of octahydropy-razin[2,1-a:5,4-a’]diisoquinoline derivatives in human breast cancer cells. Arch. Pharm. Res. 2015, 38, 628–641. [Google Scholar] [CrossRef]
- Gornowicz, A.; Bielawska, A.; Czarnomysy, R.; Gabryel-Porowska, H.; Muszyńska, A.; Bielawski, K. The combined treatment with novel platinum(II) complex and anti-MUC1 increases apoptotic response in MDA-MB-231 breast cancer cells. Mol. Cell. Biochem. 2015, 408, 103–113. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Czajkowska, A.; Gornowicz, A.; Pawłowska, N.; Czarnomysy, R.; Nazaruk, J.; Szymanowski, W.; Bielawska, A.; Bielawski, K. Anticancer Effect of a Novel Octahydropyrazino[2,1-a:5,4-a′]diisoquinoline Derivative and Its Synergistic Action with Nigella sativa in Human Gastric Cancer Cells. BioMed Res. Int. 2017, 2017, 1–13. [Google Scholar] [CrossRef] [PubMed]
- Gornowicz, A.; Pawłowska, N.; Czajkowska, A.; Czarnomysy, R.; Bielawska, A.; Bielawski, K.; Michalak, O.; Staszewska-Krajewska, O.; Kałuża, Z. Biological evaluation of octahydropyrazin[2,1-a:5,4-a′]diisoquinoline derivatives as potent anticancer agents. Tumor Biol. 2017, 39, 1010428317701641. [Google Scholar] [CrossRef] [PubMed] [Green Version]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Gornowicz, A.; Szymanowska, A.; Mojzych, M.; Czarnomysy, R.; Bielawski, K.; Bielawska, A. The Anticancer Action of a Novel 1,2,4-Triazine Sulfonamide Derivative in Colon Cancer Cells. Molecules 2021, 26, 2045. https://doi.org/10.3390/molecules26072045
Gornowicz A, Szymanowska A, Mojzych M, Czarnomysy R, Bielawski K, Bielawska A. The Anticancer Action of a Novel 1,2,4-Triazine Sulfonamide Derivative in Colon Cancer Cells. Molecules. 2021; 26(7):2045. https://doi.org/10.3390/molecules26072045
Chicago/Turabian StyleGornowicz, Agnieszka, Anna Szymanowska, Mariusz Mojzych, Robert Czarnomysy, Krzysztof Bielawski, and Anna Bielawska. 2021. "The Anticancer Action of a Novel 1,2,4-Triazine Sulfonamide Derivative in Colon Cancer Cells" Molecules 26, no. 7: 2045. https://doi.org/10.3390/molecules26072045
APA StyleGornowicz, A., Szymanowska, A., Mojzych, M., Czarnomysy, R., Bielawski, K., & Bielawska, A. (2021). The Anticancer Action of a Novel 1,2,4-Triazine Sulfonamide Derivative in Colon Cancer Cells. Molecules, 26(7), 2045. https://doi.org/10.3390/molecules26072045