Molecular docking and simulation studies of squalene obtained from Amaranthus Hybridus with DNA topoisomerase II alpha

*Article not assigned to an issue yet

, , , ,


Research Articles | Published:

Print ISSN : 0970-4078.
Online ISSN : 2229-4473.
Website:www.vegetosindia.org
Pub Email: contact@vegetosindia.org
Doi: 10.1007/s42535-023-00759-2
First Page: 0
Last Page: 0
Views: 1290


Keywords: n Amaranthus Hybridusn , Squalene, Anticancerous properties, Human DNA topoisomerases, Molecular docking


Abstract


DNA-Topoisomerases (DNA-Topo) are universal nuclear enzymes which deal with the DNA topology during cellular activities. These are the important and novel drug targets for several severe cancer drugs. Topo inhibitors interact to the (DNA-Topo) complex and restrain DNA duplication procedure. An assortment of potential inhibitors of DNA-TopoI/II complex is recommended as anti-cancerous drugs. Topo II is implicated as a significant and considerable target for the development and improvement of novel drugs having anticancerous potential. Previously, the compound squalene has been isolated and reported from Amaranthus Hybridus using GC-MS analysis and here we demonstrated in silico molecular docking and simulation studies of squalene with human Topo II alpha. This study showed that squalene has good binding affinity and shows hydrophobic interactions with Topo II alpha. Hence, squalene may have inhibitory effect on Topo II alpha as it is attaching near its active site. Several amino acid residues of the enzyme (Topo II alpha) are implicated in binding with squalene. According to our findings, squalene could be reconstructed as a Topo II alpha determent and approved as an anti-cancerous medicine. Further, to validate its efficacy design of in vitro and in vivo experiments is required.


n              Amaranthus Hybridusn            , Squalene, Anticancerous properties, Human DNA topoisomerases, Molecular docking


*Get Access

(*Only SPR Members can get full access. Click Here to Apply and get access)

Advertisement

References


An X, Xu F, Luo R, Zheng Q et al (2018) The prognostic significance of topoisomerase II alpha protein in early stage luminal Breast cancer. BMC Cancer 18(1):331


Bekker H, Berendsen HJC et al (1993) In: Groot RAD, Nadrchal J (eds) Gromacs: a parallel computer for molecular dynamics simulations. Physics computing 92. World Scientific, Singapore, pp 252–256


Bertozzi D, Marinello J, Manzo SG, Fornari F, Gramantieri L, Capranico G (2014) The natural inhibitor of DNA topoisomerase I, camptothecin, modulates HIF- 1α activity by changing miR expression patterns in human cancer cells. Mol Cancer Ther 13(1):239–248


Bhilwade HN, Tatewaki N, Giridharan VV, Nishida H, Konishi T (2010) Modulation of doxorubicin-induced genotoxicity by squalene in Balb/c mice. Food Funct 1:174–179


Bhilwade HN, Tatewaki N, Konishi T, Nishida M et al (2019) The adjuvant effect of Squalene, an active ingredient of Functional Foods, on Doxorubicin-treated allograft mice. Nutr Cancer 71:1153–1164


Budin JT, Breene WM, Putnam DH (1996) Some compositional properties of seeds and oils of eight Amaranthus species. J Assoc Oil Chem Soc 73:475


Champoux JJ (2001) DNA topoisomerases: structure, function and mechanism. Annu Rev Biochem 70:369–413


DeLano WL (2002) Pymol: an open-source molcular graphics tool. CCP4. Newsl Protein Crystallogr 40:82–92


Depowski PL, Rosenthal SI, Brien TP, Stylos S, Johnson RL, Ross JS (2000) Topoisomerase IIα expression in Breast cancer: correlation with outcome variables. Mod Pathol 13(5):542–547


Drwal MN, Agama K, Pommier Y, Griffith R (2013) Development of purely structure-based pharmacophores for the topoisomerase I-DNA-ligand binding pocket. J Comput Aided Mol Des 27(12):1037–1049


Du X, Li Y, Xia YL, Ai SM, Liang J, Sang P, Ji XL, Liu SQ (2016) Insights into protein–ligand interactions: mechanisms, models and methods. Int J Mol Sci 17:144


Ghimire GP, Nguyen HT, Koirala N, Sohng JK (2016) Advances in biochemistry and microbial production of squalene and its derivatives. J Microbiol Biotechnol 26(3):441–451


Heck MM, Earnshaw WC (1986) Topoisomerase II: a specific marker for cell proliferation. J Cell Biol 103:2569–2581


Hess B, Bekker H, Berendsen HJ, Fraaije JG (1997) LINCS: a linear constraint solver for molcular simulations. J Comput Chem 18(12):1463–1472


Hevener K, Verstak TA, Lutat KE, Riggsbee DL, Mooney JW (2018) Recent developments in topoisomerase-targeted cancer chemotherapy. Acta Pharm Sin B 8(6):844–861


Hsiang YH, Hertzberg R, Hecht S, Liu LF (1985) Camptothecin induces protein-linked DNA breaks via mammalian DNA topoisomerase I. J Biol Chem 260:14873–14878


Huang ZR, Lin YK, Fang JY (2009) Biological and pharmacological activities of squalene and related compounds: potential uses in cosmetic dermatology. Molecules 14(1):540–554


Jahaniaval F, Kakuda Y, Marcone MF (2000) Fatty acid and triacylglycerol compositions of seed oils of five Amaranthus accessions and their comparison to other oils. JAOCS 77(8)


Jo S, Kim T, Iyer VG, Im W (2008) CHARMM-GUI: a web-based graphical user interface for CHARMM. J Comput Chem 29:1859–1865


Kelly GS (1999) Squalene and its potential clinical uses. Altern Med Rev 4(1):29–36


Kim SK, Karadeniz F (2012) Biological importance and applications of squalene and squalane. Adv Food Nutr Res 65:223–233


Kitdumrongthum, Sarunya et al (2020) Inhibition of topoisomerase IIα and induction of DNA damage in cholangiocarcinoma cells by altholactone and its halogenated benzoate derivatives. Biomed Pharmacother 127:110149


Kumar A, Bora U (2014) Molecular docking studies of curcumin natural derivatives with DNA topoisomerase I and II-DNA complexes. Interdiscip Sci Comput Life Sci 6(4):285–291


Lozano-Grande MA, Gorinstein S, Espitia-Rangel E, Dávila-Ortiz G, Martínez-Ayala AL (2018) Plant sources, extraction methods and uses of Squalene. Hindawi Int J Agron 13 pages


Marinello J, Chillemi G, Bueno S, Manzo SG, Capranico G (2013) Antisense transcripts enhanced by camptothecin at divergent CpG-island promoters associated with bursts of topoisomerase I-DNA cleavage complex and R-loop formation. Nucleic Acids Res 41:10110–10123


Murakoshi M, Nishino H, Tokuda H, Iwashima A, Okuzumi J et al (1992) Inhibition by squalene of the tumor-promoting activity of 12-O-tetradecanoylphorbol-13-acetate in mouse-skin carcinogenesis. Int J Cancer 52:950–952


Nakagawa M, Yamaguchi T, Fukawa H, Ogata J, Komiyama S et al (1985) Potentiation by squalene of the cytotoxicity of anticancer agents against cultured mammalian cells and murine Tumor. Jpn J Cancer Res 76:315–320


Nelson EM, Tewey KM, Liu LF (1984) Mechanism of antitumor drug action: Poisoning of mammalian DNA topoisomerase II on DNA by 4′-(9-acridinylamino)-methanesulfon-m-anisidide. Proc Natl Acad Sci USA 81:1361–1365


Nitiss JL (2009) Targeting DNA topoisomerase II in cancer chemotherapy. Nat Rev Cancer 9:338–350


Pham DM, Boussouira B, Moyal D, Nguyen QL (2015) Oxidization of squalene, a human skin lipid: a new and reliable marker of environmental pollution studies. Int J Cosmet Sci 37(4):357–365


Pires DEV, Blundell TL, Ascher DB (2015) pkCSM: Predicting Small-Molecule Pharmacokinetic and Toxicity properties using graph-based signatures. J Med Chem 58:4066–4072


Ramirex D, Caballero J (2016) Is it reliable to use common molcular docking methods for comparing the binding affinities of Enantiomer pairs for their protein target. Int J Mol Sci 17:525


Rao CV, Newmark HL, Reddy BS (1998) Chemopreventive effect of squalene on colon Cancer. Carcinogenesis 19:287–290


Sachs L (1996) The control of hematopoiesis and Leukemia: from basic biology to the clinic. Proc Natl Acad Sci USA 93:4742–4749


Salerno S, Settimo FD, Taliani S, Simorini F, La Motta C, Fornaciari G, Marini AM (2010) Recent advances in the development of dual topoisomerase I and II inhibitors as anticancer Drugs. Curr Med Chem 17(35):4270–4290


Schnetzler KA, Breene WM (1994) Food uses and amaranth product research: a comprehensive review. In: O. Peredes-López (ed.) Amaranth Biology, Chemistry and Technology 155–184


Sharma H, Vijayvergia R (2019) Phytochemical screening and GC-MS analysis of bioactive compounds obtained from Amaranthus Hybridus. Int Res J of Pharm 10(9):187–190


Smith TJ (2000) Squalene: potential chemopreventive agent. Exp Opin Investig Drugs 9:1841–1848


Smith TJ, Yang GY, Seril DN, Liao J, Kim S (1998) Inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanone-induced lung tumorigenesis by dietary olive oil and squalene. Carcinogenesis 19:703–706


Staker BL, Hjerrild K, Feese MD, Behnke CA, Burgin AB Jr, Stewart L (2002) The mechanism of topoisomerase I Poisoning by a camptothecin analog. Proc Natl Acad Sci USA 99:15387–15392


Stella L, Melchionna S (1998) Equilibration and sampling in molecular dynamics simulations of biomolecules. J Chem Phys 109:10115–10117


Sun H, Wiesenborn D, Rayas-Duarte P, Mohamed A, Hagen K (1995) Bench-scale processing of amaranth seed for oil. J Assoc Oil Chem Soc 72:1551


Sun H, Wiesenborn D, Tostenson K, Gillespie J, Rayas-Duarte P (1997) Fractionation of squalene from amaranth seed oil. J Assoc Oil Chem Soc 74:413–418


Wang JC (2002) Cellular roles of DNA topoisomerases: a molecular perspective. Nat Rev Mol Cell Biol 3:430–440


Wang S, Miller W, Milton J, Vicker N, Stewart A et al (2002) Structure-activity relationships for analogues of the phenazine-based dual topoisomerase I/II inhibitor XR11576. Bioorg Med Chem Lett 11(3):415–418


Wang YR, Chen SF, Wu CC et al (2017) Producing irreversible topoisomerase II-mediated DNA breaks by site-specific pt(II)-methionine coordination chemistry. Nucleic Acids Res 13(18):10861–10871


Woessner RD, Mattern MR, Mirabelli CK, Johnson RK, Drake FH (1991) Proliferation- and cell cycle-dependent differences in expression of the 170 kilodalton and 180 kilodalton forms of topoisomerase II in NIH-3T3 cells. Cell Growth Differ 2(4):209–214


Xie ZR, Hwang MJ (2015) Methods for predicting protein-ligand binding sites. Methods Mol Biol 1215:383–398


Zhang S, Liu X, Bawa-Khalfe T, Lu LS, Lyu YL, Liu LF, Yeh ET (2012) Identification of the molecular basis of doxorubicin-induced cardiotoxicity. Nat Med 18(11):1639–1642


Zhang X, Rakesh KP, Shantharam CS, Manukumar HM, Asiri AM et al (2018) Podophyllotoxin derivatives as an excellent anticancer aspirant for future chemotherapy: a key current imminent needs. Bioorg Med Chem 26:340–355

 


Acknowledgements


The authors are duly grateful to RUSA 2.0 Programme for providing good research facilities and financial support.


Author Information


Pareek Shruti Shree
Plant Pathology and Biochemistry Laboratory, Department of Botany, University of Rajasthan, Jaipur, India

Vijayvargia Pratima
Plant Pathology and Biochemistry Laboratory, Department of Botany, University of Rajasthan, Jaipur, India


Jha Saroj Kumar
Plant Pathology and Biochemistry Laboratory, Department of Botany, University of Rajasthan, Jaipur, India


Khandelwal Deepika
Plant Pathology and Biochemistry Laboratory, Department of Botany, University of Rajasthan, Jaipur, India


Vijayvergia Rekha
Plant Pathology and Biochemistry Laboratory, Department of Botany, University of Rajasthan, Jaipur, India
rekhavijay1367@gmail.com