Phytochemical and Biomedical Analysis of β-cyclocitral Extracted from Galium mite (Medicinal Herb), and its Effects on Breast Cancer Targeted Proteins

Document Type : Research Paper

Authors

1 Plant Bioproducts Department, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran

2 Biology Department, Ardabil Branch, Islamic Azad University, Ardabil, Iran

3 Molecular Medicine Department, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran

Abstract

Molecular docking PyRx software coupled with gas chromatography/mass spectrometry (GC-MS) was used to identify predicted proteins which were targeted by β-cyclocitral derived from Galium mite var. roseum Ghahr. Twenty-four phytochemical compounds were detected using the GC-MS technique. Physiochemical qualities of β-cyclocitral were done using Pubchem database. Pharmaceutical and pharmacokinetic properties of the extracted β-cyclocitral were evaluated using SwissADME and GeneCards databases. One hundred entries were determined in this query. Molecular docking properties were implemented using PyRx software. Results indicated that twenty-two of these entries were predicted to be candidate as target proteins in breast cancer treatment. Catepsin k, Andregone receptor, Alcohol dehydrogenase alpha chain, Cytochrome P450 17A1 and Prostaglandin E synthase with binding affinity of 6.5, 6.2, 6, 5.7, and 5.7kcal/mol, exhibited the highest binding affinity with target proteins respectively. The project results revealed that β-cyclocitral could be used as a ligand in targeting proteins evolved in breast cancer.

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References

  1. . Harirchi I., Kolahdoozan S., Karbakhsh M., Chegini N., Mohseni S.M., Montazeri A., Momtahen A.J., Kashefi A., Ebrahimi M. Twenty years of breast cancer in Iran: down staging without a formal screening program. Ann Oncol. 2011; 22: 93-97.
  2. Ferlay J., Colombet M., Soerjomataram I., Mathers C., Parkin D., Pineros M., Znaor A., & Bray F. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer. 2019; 144:1941–1953.
  3. Lester J. Breast cancer in 2007: Incidence, risk assessment and risk reduction strategies. Clinical J Oncology Nursing. 2007; 11:619–622.
  4. Singh P., Raj R., Kumar V., Mahjan M.P., Bedi PMS., Kaur T. 1, 2, 3-Triazole tethered b-lactam-chalconebifunctional hybrids:synthesis and anticancer evaluation. Eur J Med Chem. 2012; 47:594-600.
  5. Sirvastava V., Negi A.S., Kumar J.K., Gupta M.M., Khanuja S.P. Plant-based anticancer molecules: achemical and biological profile of some importantleads. Bioorg Med Chem. 2005; 13:5892-5908.
  6. Javidnia K., Jafari A., Shahabipour S., Afshaki S. Chemical constituents of the essential oil of Galium mite var. roseum ghahramaninejad. Chem Natural Compounds. 2014. DOI: 10.1007/s10600-014-1119-1.
  7. Gambliel H.A., Cates R.G. Terpene changes due to maturation and canopy level in Douglas-fir (Pseudotsugamenziesii) flush needle oil. Biochem. Syst. Ecol. 1995; 23:469–476.
  8. Guimarães A.G., Quintans J.S., Quintans, L.J. Monoterpenes with analgesic activity-a systematic review. Phytother, 2013; 27: pp.1–15.
  9. Turek C., Stintzing F.C. Stability of Essential Oils: A Review. Compr. Rev. Food Sci. Food Saf. 2013;12:40–53.
  10. Bardon S., Foussard V., Fournel S., Loubat A. Monoterpenes inhibit proliferation of human colon cancer cells by modulating cell cycle-related protein expression. Cancer Lett. 2002; 181: 187–94.
  11. Havaux M. Carotenoid oxidation products as stress signals in plants. The plant journal. 2013; 79:597-606.
  12. Zhao C., Song X., Liu Y. Synthesis of graphene quantum dots and their applications in drug delivery. J Nanobiotechnol. 2020. Doi: 10.1186/s12951-020-00698-z.
  13. Gilardi G. Impact of R264C and R264H polymorphisms in human aromatase function. The Journal of Steroid Biochemistry and Molecular Biology. 2017; 167:23-32.
  14. Anderson S., Russell D.W. Structural and biochemical properties of cloned and expressed human and rat steroid 5alpha-reductases. Biochemistry Proc. Natl. Acad. Sci. USA. 1990; 87: 3640-3644.
  15. McDonell P.B. The Opposing Transcriptional Activities of the Two Isoforms of the Human Progesterone Receptor Are Due to Differential Cofactor Binding. Molecular and Cellular Biology. 2000; 20:3102-15.
  16. Gaudet P. Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in Bioinformatics. 2011;12:449-462.
  17. Yang J. The single-macro domain protein LRP16 isan essential cofactor of androgen receptor. Endocrine related cancer. 2009; 16: 139-153.
  18. Ston C.L., Li T., Bosron W.F. Stereospecific Oxidation of Secondary Alcohols by Human Alcohol Dehydrogenase. Journal of biological chemistry. 1989; 264:11112-11116.
  19. Jegerschoold C. Structural basis for induced formation of theinflammatory mediator prostaglandin E2. 2008. Doi:10.1073/pnas.0802894105.
  20. Miller W.L. Cytochrome b5 augments the 17, 20-Lyase Activity of Human P450c17 without Direct Electron Transfer. J Biological Chem.1998; 273:3158–3165.
  21. Wang B. Activation of EphA2 kinase suppresses integrin function and causes focal-adhesion-kinase dephosphorylation. Nature Cell Biology. 2000; 2: pp.62–69.
  22. Barnett J. Purification, characterization and selective inhibition of human prostaglandin G/H synthase 1 and 2 expressed in the baculovirus system. Biochimica et BiophysicaActa (BBA)- Protein Structure and Molecular Enzymology. 1994; 1209:130-139.
  23. Lambert J.C. ADAM30 Downregulates APP-Linked Defects ThroughCathepsin D Activation in Alzheimer's disease. EbioMedicine. 2016; 9:278-292.
  24. Molli P.R., Singh R.R., Lee S.W., Kumar R. MTA1-mediated transcriptional repression of BRCA1 tumor suppressor gene. Nature. 2008; 14:1971–1980.
  25. Koyama S. Repression of estrogen receptor β function by putative tumor suppressor DBC1. Biochemical and Biophysical Research Communications. 2010; 392:357-362.
  26. Drake R.R. In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine. Proteomics, 2013; 13:1667-1671.
  27. Sacchettini J.C. Structural studies on human muscle fatty acid binding protein at 1.4A resolution: binding interactions with three C18 fatty acids. Structure.1994; 2:523-534.
  28. Maryuma T., Nara K., Yoshikawa H., Suzuki N. Txk, a member of the non-receptor tyrosine kinase of the Tec family, forms a complex with poly (ADP-ribose) polymerase 1 and elongation factor 1α and regulates interferon-γ gene transcription in Th1 cells. Clinical and Experimental Immunology. 2007; 147:164–175.
  29. Tepel C., Bromme D., Herzog V., Brix K. Cathepsin K in thyroid epithelial cells: sequence, localization and possible function in extracellular proteolysis of thyroglobulin. J Cell Sci. 2000; 113 (24):4487–4498.
  30. De Simone, G. Carbonic anhydrase inhibitors: Binding of an antiglaucomaglycosyl-sulfanilamide derivative to human isoform II and its consequences for the drug design of enzyme inhibitors incorporating sugar moieties. Bioorganic & Med Chem Letters. 2007; 17:1726-1731.
  31. Lebioda L. Structure of Human Thymidylate Synthase Suggests Advantages of Chemotherapy with Noncompetitive Inhibitors. Biology Chem. 2001; 276:14170–14177.
  32. Ojala P. Application of Active and Kinase-Deficient Kinome Collection for Identification of Kinases Regulating Hedgehog Signaling. Cell. 2008; 133:537-548.
  33. Demple, B. Covalent Trapping of Human DNA polymerase by the Oxidative DNA Lesion 2-Deoxyribonolactone. Journal of biological chemistry. 2002; 277:7637-7640.
  34. Decarolis E., Denis D., Riendeau D. Oxidative Inactivation of Human 5-Lipoxygenase in Phosphatidylcholine vesicles. Eur. J. Biochem, 1996; 235: 416-423.
Journal of Medicinal plants and By-products
Volume 14, Issue 3
May and June 2025
Pages 238-244

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