Virtual screening and assessment of anticancer potential of selenium-based compounds against HL-60 and MCF7 cells
Abstract
Aim: Selenium-based compounds have antitumor potential. We used a ligand-based virtual screening analysis to identify selenoglycolicamides with potential antitumor activity. Results & Conclusion: Compounds 3, 6, 7 and 8 were selected for in vitro cytotoxicity tests against various cell lines, according to spectrophotometry results. Compound 3 presented the best cytotoxicity results against a promyelocytic leukemia line (HL-60) and was able to induce cell death at a frequency similar to that observed for doxorubicin. The docking study showed that compound 3 has good interaction energies with the targets caspase-3, 7 and 8, which are components of the apoptotic pathway. These results suggested that selenium has significant pharmacological potential for the selective targeting of tumor cells, inducing molecular and cellular events that culminate in tumor cell death.
Graphical abstract
Papers of special note have been highlighted as: • of interest; •• of considerable interest
References
- 1. . Selenium compounds and apoptotic modulation: a new perspective in cancer therapy. Mini Rev. Med. Chem. 8(10), 1020–1031 (2008). • Describes epidemiological data on cancer worldwide.
- 2. . Selenium compounds, apoptosis and other types of cell death: an overview for cancer therapy. Int. J. Mol. Sci. 13(8), 9649–9672 (2012).
- 3. . The global and regional burden of cancer. World Cancer Rep. 1, 16–53 (2014).
- 4. . A systematic review of worldwide incidence of nonmelanoma skin cancer. Br. J. Dermatol. 166(5), 1069–1080 (2012).
- 5. . Oncologia: Bases Clínicas do Tratamento. Guanabara, Rio de Janeiro, Brazil, 41–42 (1996).
- 6. . Hallmarks of cancer: the next generation. Cell 144(5), 646–674 (2011).
- 7. . Terapêutica Oncológica Para Enfermeiros e Farmacêuticos. Atheneu, São Paulo, Brazil, 644–645 (2012).
- 8. Cancer treatment and survivorship statistics, 2012. CA Cancer J. Clin. 62(4), 220–241 (2012).
- 9. . Physiological modulation approaches to improve cancer chemotherapy: a review. Anticancer Agents Med. Chem. 14(5), 713–749 (2014). • Describes studies that report antitumor activity of some compounds containing selenium.
- 10. . Adverse health effects of selenium in humans. Rev. Environ. Health 16(4), 233–260 (2001).
- 11. . Is selenium a potential treatment for cancer metastasis? Nutrients 5(4), 1149–1168 (2013).
- 12. . Selenium and human health. Lancet 379(9822), 1256–1268 (2012).
- 13. . Selenium metabolism in cancer cells: the combined application of XAS and XFM techniques to the problem of selenium speciation in biological systems. Nutrients 5(5), 1734–1756 (2013).
- 14. . Evaluation of mutagenic activity of the organo-selenium compound Selol by use of the Salmonella typhimurium mutagenicity assay. Mutat. Res. Genet. Toxicol. Environ. Mutagen. 699(1–2), 44–46 (2010). • Addresses the importance of computer-aided drug design in the development of new drugs.
- 15. Novel chemotypes targeting tubulin at the colchicine binding site and unbiasing P-glycoprotein. Eur. J. Med. Chem. 139, 792–803 (2017).
- 16. Docking-based classification models for exploratory toxicology studies on high-quality estrogenic experimental data. Future Med. Chem. 7(14), 1921–1936 (2015).
- 17. . In silico studies applied to natural products with potential activity against Alzheimer's disease. In: Computational Modeling of Drugs Against Alzheimer’s Disease. Springer, NY, USA, 513–531 (2018).
- 18. Computer-aided drug design studies in food chemistry. In: Natural and Artificial Flavoring Agents and Food Dyes. Elsevier, MA, USA, 261–297 (2018).
- 19. . Predictive ecotoxicity of MoA 1 of organic chemicals using in silico approaches. Ecotoxicol. Environ. Saf. 153, 151–159 (2018). •• Describes the synthetic methodology and data that helped characterize the compounds used in the study.
- 20. Combined structure-and ligand-based virtual screening aiding discovery of selenoglycolicamides as potential multitarget agents against Leishmania species. J. Mol. Struct. 1198, 126872 (2019). •• Describes methodologies of good practice in data curation for use in virtual screening.
- 21. . Trust, but verify: on the importance of chemical structure curation in cheminformatics and QSAR modeling research. J. Chem. Inf. Model. 50(7), 1189–1204 (2010).
- 22. . Curation of chemogenomics data. Nat. Chem. Biol. 11(8), 535–535 (2015).
- 23. . Trust, but verify II: a practical guide to chemogenomics data curation. J. Chem. Inf. Model. 56(7), 1243–1252 (2016).
- 24. Per aspera ad astra: application of Simplex QSAR approach in antiviral research. Fut. Med. Chem. 2(7), 1205–1226 (2010).
- 25. . Random forests. Mach. Learn. Springer, USA, 45(1), 5–32 (2001).
- 26. . The WEKA data mining software: an update. SIGKDD Explor. 11(1), 10–18 (2009).
- 27. . The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology 143(1), 29–36 (1982). •• Relevant works to elucidate the results obtained in our in vitro studies of anticancer activity.
- 28. . Tunable allosteric library of caspase-3 identifies coupling between conserved water molecules and conformational selection. Proc. Natl Acad. Sci. 113(41), E6080–E6088 (2016).
- 29. The three-dimensional structure of caspase-8: an initiator enzyme in apoptosis. Structure 7(9), 1125–1133 (1999).
- 30. . L2′ loop is critical for caspase-7 active site formation. Protein Sci. 18(7), 1459–1468 (2009).
- 31. . Evaluations of molecular docking programs for virtual screening. J. Chem. Inf. Model. 47(4), 1609–1618 (2007).
- 32. . MolDock: a new technique for high-accuracy molecular docking. J. Med. Chem. 49(11), 3315–3321 (2006).
- 33. Cell viability assays. In: Assay Guidance Manual. Eli Lilly & Company and the National Center for Advancing Translational Sciences (2016).
- 34. . Estudo do potencial anticâncer de um derivado de Chalcona, 1-(4-Nitrofenil)-3-Fenilprop-2-En-1-Ona, in vitro e in vivo. Master Dissertation 1, 170 (2010).
- 35. . Dual AO/EB staining to detect apoptosis in osteosarcoma cells compared with flow cytometry. Med. Sci. Monit. 21, 15 (2015).
- 36. . JC-1: alternative excitation wavelengths facilitate mitochondrial membrane potential cytometry. Cell Death Dis. 3, e430 (2012).
- 37. . Selenium in cancer prevention: a review of the evidence and mechanism of action. Proc. Nutr. Soc. 64(4), 527–542 (2005).
- 38. . The sulphorhodamine (SRB) assay and other approaches to testing plant extracts and derived compounds for activities related to reputed anticancer activity. Methods 42(4), 377–387 (2007).
- 39. . Selenium compounds as therapeutic agents in Cancer. Biochim. Biophys. Acta 1850(8), 1642–1660 (2015).
- 40. . Anticancer potential of aqueous ethanol seed extract of Ziziphus mauritiana against cancer cell lines and Ehrlich ascites carcinoma. Evid. Based Complement. Alternat. Med. e-pub (2011).
- 41. . Quimioterapia antineoplásica: revisão da literatura. Rev. Min. Enferm. 3(1/2), 60–67 (1999).
- 42. . Four deaths and a funeral: from caspases to alternative mechanisms. Nat. Rev. Mol. Cell Biol. 2, 589–598 (2001).
- 43. Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009. Cell Death Differ. 16(1), 3–11 (2009).
- 44. . Targeting apoptotic and autophagic pathways for cancer therapeutics. Cancer Lett. 300(2), 105–114 (2011).
- 45. . Formation of methylselenol, dimethylselenide and dimethyldiselenide in in vitro metabolism models determined by headspace GC-MS. Metallomics 2(2), 167–173 (2010).
- 46. . Selenium compounds activate early barriers of tumorigenesis. J. Biol. Chem. 285(16), 12055–12062 (2010).
- 47. . Mitochondria in apoptosis: past, present and future. Biochem. Soc. Trans. 32(3), 493–495 (2004).
- 48. Selenium in human health and disease. Antiox. Redox Sign. 14(7), 1337–1383 (2011).
- 49. . Mitochondrial apoptosis: killing cancer using the enemy within. Br. J. Cancer 112(6), 957–962 (2015).
- 50. A novel thioredoxin reductase inhibitor inhibits cell growth and induces apoptosis in HL-60 and K562 cells. J. Zhejiang Univ. Sci. B 9(1), 16–21 (2008).
- 51. . The BCL-2 protein family: opposing activities that mediate cell death. Nat. Rev. Mol. 9(1), 47–59 (2008).
- 52. . The morphology of various types of cell death in prenatal tissues. Teratology 7(3), 253–266 (1973).
- 53. . Tumour necrosis factor-induced necrosis versus anti-Fas-induced apoptosis in L929 cells. Cytokine 9(11), 801–808 (1997).
- 54. . Interdigital cell death can occur through a necrotic and caspase-independent pathway. Curr. Biol. 9(17), S967–S961 (1999).
- 55. . The role of BCL2 family of apoptosis regulator proteins in acute and chronic leukemias. Adv. Hematol. 524308 (2012).
- 56. . From bench to clinic with apoptosis-based therapeutic agents. Nature 407(6805), 810–816 (2000).
- 57. . Apoptosis pathways in cancer and cancer therapy. Cancer Immunol. Immunother. 53(3), 153–159 (2004).
- 58. . Selenium and cancer: biomarkers of selenium status and molecular action of selenium supplements. Eur. J. Nut. 47(2), 29–50 (2008).