Abstract Views
PDF Download

Potential of natural antioxidant compound in Cymbopogon nardus as anti-cancer drug via HSP-70 inhibitor : A bioinformatics approach

, , ,
Pages 129-139


Citronella grass (Cymbopogon nardus) is a plant containing many metabolite compounds which prevent and treat various diseases, one of which is cancer. Antioxidant compounds found in citronella have been shown to improve the immune system by increasing cytokines. The activity of changing homeostasis generates free radicals. Free radicals causing protein damage so that Heat Shock Protein-70 (HSP70) is overexpressed. HSP70 has a role as a chaperon. Mutations in the anti-apoptotic protein HSP70 are one of the causes of cancer. This current research aims to determine the potential of compounds present in the citronella plant stem as anti-cancer through inhibition of HSP-70. The method was a bioinformatics approach, namely the in-silico method which provided a simulation of binding protein ligands to HSP-70 as inhibitor mechanism. The results of this study indicated that there was a potential for citronella compounds, namely spathulenol binding to HSP-70. Spathulenol compounds interact with Hsp70 via the positions Thr204, Gly12, Gly203, Thr14, Lys71, Asp10, Val369, Asp199, Val337, Gly338, Asp366, Gly339, Pro365, Glys201, & Glys202 with Van der Waals bonds and hydrogen bonds on Thr13. In the complex, there was one unfavorable bond formed on the O atom of the query ligand. From the results above, it can be concluded that the Spathulenol compound is predicted to act as an inhibitor of Hsp70 protein activity because it inhibits the binding site of the native ligand on Hsp70. The stability of the binding interaction produced by Spathulenol allows a response to Hsp70 inhibitor activity. By inhibiting the activity of Hsp70 inhibitors, it is possible to inhibit the formation and proliferation of cancer cells

There is no Figure or data content available for this article


  • Gehrmann M, Specht HM, Bayer C, Brandstetter M, Chizzali B, Duma M, et al. Hsp70 - a biomarker for tumor detection and monitoring of outcome of radiation therapy in patients with squamous cell carcinoma of the head and neck. Radiat Oncol. 2014;9:131. doi:10.1186/1748-717X-9-131.
  • Younas M, Hano C, Giglioli-Guivarc’h N, Abbasi BH. Mechanistic evaluation of phytochemicals in breast cancer remedy:current understanding and future perspectives. RSC Adv. 2018;8(52):29714-29744. doi:10.1039/C8RA04879G.
  • Nevins JR, Potti A. Mining gene expression profiles: expression signatures as cancer phenotypes. Nat Rev Genet 2007,8:601–609.
  • Lanneau D, Brunet M, Frisan E, Solary E, Fontenay M, Garrido C. Heat shock proteins: essential proteins for apoptosis regulation. J. Cell. Mol. Med. 2008;12(3):743-761. doi:10.1111/j.1582-4934.2008.00273.x.
  • Garrido C, Brunet M, Didelot C, Zermati Y, Schmitt E, Kroemer G. Heat shock proteins 27 and 70: antiapoptotic proteins with tumorigenic properties. Cell Cycle 2006;5:2592–601. doi: 10.4161/cc.5.22.3448.
  • Mosser DD, Caron AW, Bourget L, Meriin AB, Sherman MY, Morimoto RI, Massie B. The chaperone function of hsp70 is required for protection against stress-induced apoptosis. Mol Cell Biol. 2000;20:7146–59. doi:10.1128/MCB.20.19.7146-7159.2000.
  • Naderi A, Teschendorff AE, Barbosa-Morais NL, Pinder SE, Green AR, et al. A gene-expression signature to predict survival in breast cancer across independent data sets. Oncogene 2006, 26:1507–1516. doi:10.1038/sj.onc.1209920.
  • Solekha R, Setiyowati PAI, Sari CTU. Phytochemical Screening of Ethanol Extract on Stems, Leaves and Roots of Citronella Grass (Cymbopogon nardus L). 2022; 5(1);141-147. doi:10.30743/best.v5i1.5320.
  • Hartatie ES, Prihartini I, Widodo W, Wahyudi A. Bioactive Compounds of Citronella grass (Cymbopogon citratus) essential oil from different parts of the plant and distillation methods as natural antioxidant in broiler meat. IOP Conf Ser Mater Sci Eng. 2019;532(1). doi:10.1088/1757-899X/532/1/012018.
  • Li CC, Yu HF, Chang CH, Liu YT, Yao HT. Effects of citronella grass oil and citral on hepatic drug-metabolizing enzymes, oxidative stress, and acetaminophen toxicity in rats. J Food Drug Anal. 2018;26(1):432-438. doi:10.1016/j.jfda.2017.01.008.
  • Setiawati, A., Riswanto, F.D.O., Yuliani, S.H., Istyastono, E.P. Retrospective Validation of A StructureBased Virtual Screening Protocol To Identify Ligands For Estrogen Receptor Alpha and Its Application To Identify The Alpha-Mangostin Binding Pose. Indo J. Chem, 2014;14(2), 103-108. doi:10.22146/ijc.21245.
  • Setiyowati PAI, Solekha R, Negara SBSMK, Rosalina N. Immunomodulator Effect of Citronella grass Extract (Cymbopogon nardus L.) to Increase Immune Cells as a Precaution Against SARS-CoV-2. 2021. doi:10.20473/bhsj.v4i2.26619.
  • Amit Koparde A, Chandrashekar Doijad R, Shripal Magdum C. Natural Products in Drug Discovery. In: Pharmacognosy-Medicinal Plants. IntechOpen; 2019. doi:10.5772/intechopen.82860.
  • Saputra NA, Wibisono HS, Darmawan S, Pari G. Chemical composition of Cymbopogon nardus essential oil and its broad spectrum benefit. IOP Conf Ser Earth Environ Sci. 2020;415(1). doi:10.1088/1755-1315/415/1/012017.
  • Ansori ANM, Kharisma VD, Parikesit AA, Dian FA, Probojati RT, Rebezov M, Scherbakov P, Burkov P, Zhdanova G, Mikhalev A, Antonius Y, Pratama MRF, Sumantri NI, Sucipto TH, Zainul R. Bioactive Compounds from Mangosteen (Gracinia mangostana L.) as an Antiviral Agent via Dual Inhibitor Mechanism against SARS-CoV-2: An In Silico Approach. Pharmacogn J. 2022; 14(1): 85-90. doi: 10.5530/pj.2022.14.12.
  • Broni E, Kwofie SK, Asiedu SO, Miller WA 3rd, Wilson MD. A Molecular Modeling Approach to Identify Potential Antileishmanial Compounds Against the Cell Division Cycle (cdc)-2-Related Kinase 12 (CRK12) Receptor of Leishmania donovani. Biomolecules. 2021;11(3):458.doi: 10.3390/biom11030458.
  • Dibha AF, Wahyuningsih S, Kharisma VD, Ansori ANM, Widyananda, MH, Parikesit AA, Rebezov M, Matrosova Y, Artyukhova S, Kenijz N, Kiseleva M, Jakhmola V, Zainul R. Biological activity of kencur (Kaempferia galanga L.) against SARS-CoV-2 main protease: In silico study. Int J Health Sci. 2022; 6(S1): 468-480. 10.1039/x0xx00000x.
  • Giordanetto F, Tyrchan C, Ulander J. Intramolecular Hydrogen Bond Expectations in Medicinal Chemistry. ACS Med Chem Lett. 2017; 8(2): 139-142. 10.1021/acsmedchemlett.7b00002
  • Kok BP, Ghimire S, Kim W, Chatterjee S, Johns T, Kitamura S, Eberhardt J, Ogasawara D, Xu J, Sukiasyan A, Kim SM, Godio C, Bittencourt JM, Cameron M, Galmozzi A, Forli S, Wolan DW, Cravatt BF, Boger DL, Saez E. Discovery of small-molecule enzyme activators by activity-based protein profiling. Nat Chem Biol. 2020 Sep;16(9):997-1005. doi: 10.1038/s41589-020-0555-4
  • Khan T, Dixit S, Ahmad R, Raza S, Azad I, Joshi S, Khan AR. Molecular docking, PASS analysis, bioactivity score prediction, synthesis, characterization and biological activity evaluation of a functionalized 2-butanone thiosemicarbazone ligand and its complexes. J Chem Biol. 2017; 10(3): 91-104. doi: 10.1007/s12154-017-0167-y.
  • Lee CM, Yen CH, Tzeng TY, Huang YZ, Chou KH, Chang TJ, Arthur Chen YM. Androgen response element of the glycine N-methyltransferase gene is located in the coding region of its first exon. Biosci Rep. 2013 Sep 17;33(5):e00070.
  • Luqman A, Kharisma VD, Ruiz RA, Götz F. In Silico and in Vitro Study of Trace Amines (TA) and Dopamine (DOP) Interaction with Human Alpha 1-Adrenergic Receptor and the Bacterial Adrenergic Receptor QseC. Cell Physiol Biochem. 2020; 54: 888-898. doi: 10.33594/000000276.
  • Nugraha AP, Rahmadhani D, Puspitaningrum MS, Rizqianti Y, Kharisma VD, Ernawati DS. Molecular docking of anthocyanins and ternatin in Clitoria ternatea as coronavirus disease oral manifestation therapy. J Adv Pharm Technol Res. 2021; 12 (4): 362-367. doi: 10.4103/japtr.japtr_126_21.
  • C, Nugraha AP, Kharisma VD, Ansori ANM, Devijanti R, Ridwan TPSP, Ramadhani NF, Narmada IB, Ardani IGAW, Noor TNEBA. A bioinformatic approach of hydroxyapatite and polymethylmethacrylate composite exploration as dental implant biomaterial. J Pharm & Pharmacogn Res. 2021; 9(5): 746-754. doi: 10. 21.1078_9.5.746
  • Proboningrat A, Kharisma VD, Ansori ANM, Rahmawati R, Fadholly A, Posa GAV, Sudjarwo SA, Rantam FA, Achmad AB. In silico Study of Natural inhibitors for Human papillomavirus-18 E6 protein. Res J Pharm Technol. 2022; 15(3):1251-6. doi:10.52711/0974-360X.2022.00209.
  • Rietman EA, Platig J, Tuszynski JA, Lakka Klement G. Thermodynamic measures of cancer: Gibbs free energy and entropy of protein-protein interactions. J Biol Phys. 2016; 42(3): 339-50. doi:10.1007/s10867-016-9410-y.
  • Rigsby RE, Parker AB. Using the PyMOL application to reinforce visual understanding of protein structure. Biochem Mol Biol Educ. 2016 Sep 10;44(5):433-7. doi:10.1002/bmb.20966.
  • Saddala MS, Huang H. Identification of novel inhibitors for TNF?, TNFR1 and TNF?-TNFR1 complex using pharmacophore-based approaches. J Transl Med. 2019 Jul 2;17(1):215. Doi:10.1186/s12967-019-1965-5.
  • Seo JH, Park JH, Lee EJ, Vo TT, Choi H, Kim JY, Jang JK, Wee HJ, Lee HS, Jang SH, Park ZY, Jeong J, Lee KJ, Seok SH, Park JY, Lee BJ, Lee MN, Oh GT, Kim KW. ARD1-mediated Hsp70 acetylation balances stress-induced protein refolding and degradation. Nat Commun. 2016 Oct 6;7:12882. doi: 10.1111/all.13465.
  • Sharma P, Shanavas A. Natural derivatives with dual binding potential against SARS-CoV-2 main protease and human ACE2 possess low oral bioavailability: a brief computational analysis. J Biomol Struct Dyn. 2021; 39(15): 5819-5830. doi: 10.1080/07391102.2020.1794970.
  • Susanto H, Kharisma VD, Listyorini D, Taufiq A. Effectivity of Black Tea Polyphenol in Adipogenesis Related IGF-1 and Its Receptor Pathway Through In Silico Based Study. J Phys Conf Ser. 2019; 1093 (1): 012037. doi :10.1088/1742-6596/1093/1/012037.
  • Wijaya RM, Hafidzhah MA, Kharisma VD, Ansori ANM, Parikesit AA. COVID-19 In Silico Drug with Zingiber officinale Natural Product Compound Library Targeting the Mpro Protein. Makara J Sci. 2021; 25(3): 162-171. 10.7454/mss.v25i3.1244
  • Ciocca DR, Arrigo AP, Calderwood SK. Heat shock proteins and heat shock factor-1 in carcinogenesis and tumor development: an update. Arch Toxicol. 2013;87(1):19–48. doi:10.1007/s00204-012-0918-z.
  • Dakappagari N, Neely L, Tangri S, Lundgren K, Hipolito L, Estrellado A, et al. An investigation into the potential use of serum Hsp70 as a novel tumour biomarker for Hsp90 inhibitors. Biomarkers. 2010;15(1):31–8. doi:10.3109/ 13547500903261347.
  • Multhoff G, Botzler C, Wiesnet M, Müller E, Meier T, Wilmanns W, et al. A stress-inducible 72-kDa heat-shock protein (HSP72) is expressed on the surface of human tumor cells, but not on normal cells. Int J Cancer. 1995;61(2):272–9. doi: 10.1002/ijc.2910610222.
  • Ferrarini M, Heltai S, Zocchi MR, Rugarli C. Unusual expression and localization of heat-shock proteins in human tumor cells. Int J Cancer. 1992;51(4):613–9. doi: 10.1002/ijc.2910510418.
  • Hantschel M, Pfister K, Jordan A, Scholz R, Andreesen R, Schmitz G, et al. Hsp70 plasma membrane expression on primary tumor biopsy material and bone marrow of leukemic patients. Cell Stress Chaperones. 2000;5(5):438–42. PMC312874. 10.1379/1466-1268(2000)005<0438:hpmeop>2.0.co;2.
  • Aghdassi A, Phillips P, Dudeja V, Dhaulakhandi D, Sharif R, Dawra R, et al. Heat shock protein 70 increases tumorigenicity and inhibits apoptosis in pancreatic adenocarcinoma. Cancer Res. 2007;67(2):616–25. doi: 10.1158/0008-5472.CAN-06-1567.
  • Garrido C, Gurbuxani S, Ravagnan L, Kroemer G. Heat shock proteins: endogenous modulators of apoptotic cell death. Biochem Biophys Res Commun. 2001;286(3):433–42. doi:10.1006/bbrc.2001.5427.
  • Jäättelä M, Wissing D, Kokholm K, Kallunki T, Egeblad M. Hsp70 exerts its anti-apoptotic function downstream of caspase-3-like proteases. EMBO J. 1998;17(21):6124–34. doi:10.1093/emboj/17.21.6124. 11.
  • Gao Y, Han C, Huang H, Xin Y, Xu Y, Luo L, et al. Heat shock protein 70 together with its co-chaperone CHIP inhibits TNF-alpha induced apoptosis by promoting proteasomal degradation of apoptosis signal-regulating kinase1. Apoptosis. 2010;15(7):822–33. doi:10.1007/s10495-010-0495-7.
  • Yang X, Wang J, Zhou Y, Wang Y, Wang S, Zhang W. Hsp70 promotes chemoresistance by blocking Bax mitochondrial translocation in ovarian cancer cells. Cancer Lett. 2012;321(2):137–43. doi:10.1016/ j.canlet.2012.01.030.
  • Kirkegaard T, Roth AG, Petersen NH, Mahalka AK, Olsen OD, Moilanen I, et al. Hsp70 stabilizes lysosomes and reverts Niemann-Pick disease-associated lysosomal pathology. Nature. 2010;463(7280):549–53. doi:10.1038/nature08710.
  • Bayer C, Liebhardt ME, Schmid TE, Trajkovic-Arsic M, Hube K, Specht HM, et al. Validation of heat shock protein 70 as a tumor-specific biomarker for monitoring the outcome of radiation therapy in tumor mouse models. Int J Radiat Oncol Biol Phys. 2014;88(3):694–700. doi:10.1016/j.ijrobp.2013.11.008.
  • Stangl S, Varga J, Freysoldt B, Trajkovic-Arsic M, Siveke JT, Greten FR, et al. Selective in vivo imaging of syngeneic, spontaneous, and xenograft tumors using a novel tumor cell-specific Hsp70 peptide-based probe. Cancer Res. 2014;74(23):6903–12. doi:10.1158/0008-5472.CAN-14-0413.
  • Gehrmann M, Stangl S, Foulds GA, Oellinger R, Breuninger S, Rad R, et al. Tumor imaging and targeting potential of an Hsp70-derived 14-mer peptide. PLoS One. 2014;9(8):e105344. doi:10.1371/journal.pone.0105344.
There is no Supplemental content for this article.

How to Cite This

Solekha, R., Setiyowati, P. A. I., Wulandari, E. F., & Maghfuroh, L. (2022). Potential of natural antioxidant compound in Cymbopogon nardus as anti-cancer drug via HSP-70 inhibitor : A bioinformatics approach . Jurnal Teknologi Laboratorium, 11(2), 129–139. https://doi.org/10.29238/teknolabjournal.v11i2.372

Article Metrics

Download Statistics


Download data is not yet available.


Metrics Loading ...

Other Statistics

Verify authenticity via CrossMark

Copyright and Permissions

Creative Commons License

This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.

Publishing your paper with Jurnal Teknologi Laboratorium (JTL) means that the author or authors retain the copyright in the paper. JTL granted an exclusive reuse license by the author(s), but the author(s) are able to put the paper onto a website, distribute it to colleagues, give it to students, use it in your thesis etc, even commercially. The author(s) can reuse the figures and tables and other information contained in their paper published by JTL in future papers or work without having to ask anyone for permission, provided that the figures, tables or other information that is included in the new paper or work properly references the published paper as the source of the figures, tables or other information, and the new paper or work is not direct at private monetary gain or commercial advantage.

JTL journal provides immediate open access to its content on the principle that making research freely available to the public supports a greater global exchange of knowledge. This journal is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License. This license lets others remix, transform, and build upon the material for any purpose, even commercially.

JTL journal Open Access articles are distributed under this Creative Commons Attribution-ShareAlike 4.0 International License (CC BY-SA). Articles can be read and shared for All purposes under the following conditions:

  • BY: You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
  • SA:  If you remix, transform, or build upon the material, you must distribute your contributions under the same license as the original.

Data Availability