Molecular Mechanism of Inhibition of Cell Proliferation: An In Silico Study of the Active Compounds in Curcuma longa as an Anticancer

https://doi.org/10.22146/jtbb.74905

Selliana Maretha Wijaya Kusuma(1), Didik Huswo Utomo(2), R Susanti(3*)

(1) Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Negeri Semarang, Jalan Taman Siswa, Kampus Sekaran, Gunungpati, Semarang, Central Java 50229, Indonesia
(2) Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan.
(3) Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Negeri Semarang, Jalan Taman Siswa, Kampus Sekaran, Gunungpati, Semarang, Central Java 50229, Indonesia
(*) Corresponding Author

Abstract


Cancer is one of the death causes in the world. Many plants act as anticancer, one of them is Curcuma longa. The purpose of this study was to analyze the molecular mechanism of compounds in Curcuma longa as an anticancer using in silico. These research methods included exploration of the active compounds of Curcuma longa plants, prediction of their activity, human intestinal absorption test, test of Lipinski's rule of five, molecular docking, and interactions of receptor with compounds as well as signaling pathways. The results showed that Curcuma longa had 20 compounds that have the potential as an anticancer. As many as 5 of the 20 active compounds, namely α-curcumene, curcumenol, curcumin, curcumin II, and curcumin III had a value of Pa > 0.3 and HIA above 80%. The results of molecular docking of α-curcumene, curcumenol, curcumin, curcumin II, and curcumin III compounds with protein receptors of VEGFR-2, EGFR, and FGFR-1 showed ∆Gbind values of -5.0 to -7.5 kcal/mol. The compound in Curcuma longa that had the most effective activity as an anticancer was curcumin with a ∆Gbind value of -7.5 kcal/mol at the FGFR-1 receptor. Curcumin molecular mechanism as antiproliferative was revealed computationally through inhibition of the PI3K/AKT/mTOR pathway.


Keywords


Anticancer, Curcuma longa, Curcumin, In silico, PI3K/AKT/mTOR pathway

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References

Abdurrahman, N., 2019. Kurkumin pada Curcuma longa sebagai Tatalaksana Alternatif Kanker (Curcumin in Curcuma longa as an Alternative Cancer Treatment). Journal Agromedicine, 6(2), pp.410-415.

American Cancer Society, 2016. Cancer Fact and Figure. Atlanta: American Cancer Society Inc.

Anand, T. & Gokulakrishnan, K., 2014. GC-MS Analysis and Anti-Microbal Activity of Bioactive Components of Hybanthus enneaspermus. International Journal of Pharmacy and Pharmateucal Science, 2(3), pp.646-650.

Anisa, D.N., Anwar, C. & Afriyani, H., 2020. Sintesis Senyawa Analog Kurkumin Berbahan Dasar Veratraldehida Dengan Metode Ultrasound. Analit: Analytical and Environmental Chemistry, 5(01), pp.74-81. doi: 10.23960%2Faec.v5i1.2020.p74-81

Arfi, A.S., Lestari, R.D. & Damayanti, D.S., 2020. Studi In Silico Senyawa Aktif Rimpang Kunyit (Curcuma domestica) terhadap Penghambatan Acetylcholinesterase, Microtubulin (Beta tubulin), dan Aktivasi Calcium channel sebagai Terapi Antelmintik. (In Silico Study: Active Compound of Turmeric Rhizome (Curcuma domestica) Towards Acetylcholinesterase and Microtubulin (Beta Tubulin) Inhibition, and Calcium Channel Activation as an Anthelmintic Therapy). Jurnal Kedokteran Komunitas, 8(2), pp.36-47.

Arwansyah, A., Ambarsari, L. & Sumaryada, T.I., 2014. Simulasi Docking Senyawa Kurkumin dan Analognya Sebagai Inhibitor Reseptor Androgen pada Kanker Prostat. Current Biochemistry, 1(1), pp.11-19. doi: 10.29244/cb.1.1.11-19

Astolfi, A. et al., 2020. The Emerging Role of the FGF/FGFR Pathway in Gastrointestinal Stromal Tumor. International Journal of Molecular Science, 27(3313), pp.1-14. doi: 10.3390/ijms21093313

Bintari, Y.R., 2018. Studi In Silico Potensi Ekstrak Lipida Tetraselmis chuii sebagai Antioksidan. Jurnal Ketahanan Pangan, 2(1), pp.76-81.

Cas, M.D. & Ghidoni, R. 2019. Dietary Curcumin: Correlation Between Bioavailability and Health Potential. Nutrients, 11(2147), pp.1-14. doi: 10.3390/nu11092147

Chamata, Y., Watson, K.A. & Jauregi, P., 2020. Whey-Derived Peptides Interactions with Ace by Molecular Docking as A Potential Predictive Tool of Natural Ace Inhibitors. International Journal of Molecular Sciences, 21(3), pp.1-13. doi: 10.3390/ijms21030864

Chao, I.C. et al., 2018. Simultaneous Quantification of Three Curcuminoids and Three Volatile Components of Curcuma longa Using Pressurized Liquid Extraction and High-Performance Liquid Chromatography. Molecules, 23(7), pp.1568. doi: 10.3390/molecules23071568

Cidado, J. & Park, B.H., 2012. Targeting the PI3K/Akt/mTOR Pathway for Breast Cancer Therapy. Journal Mammary Gland Biology and Neoplasia, 17(3-4), pp.205-216. doi: 10.1007/s10911-012-9264-2

Dallakyan, S. & Olson, A.J., 2014. Small-Molecule Library Screening by Docking with PyRx. Methods in Molecular Biology, 1263, pp.243-250. doi: 10.1007/978-1-4939-2269-7_19

Devassy, J., Nwachukwu, I. & Jones, P., 2015. Curcumin and Cancer: Barriers to Obtaining a Health Claim. Nutrition Reviews, 73(3), pp.155-165. doi: 10.1093/nutrit/nuu064

Druzhilovskiy, D. S. et al., 2016. Online Resources for the Prediction of Biological Activity of Organic Compounds. Russian Chemical Bulletin, 65(2), pp.384-393. doi: 10.1007/s11172-016-1310-6

Ezealisiji, K.M. & Awucha, N.E., 2020. Phytochemistry and GC-MS analysis of methanolic leaf extract of Newbouldia leavis (Bignonacea). Journal of Pharmacognosy and Phytochemistry, 9(2), pp.1998-2004.

Filimonov, D.A. et al., 2014. Prediction of the Biological Activity Spectra of Organic Compounds Using the PASS Online Web Resource. Chemistry of Heterocyclic Compounds, 50(3), pp.444-457. doi: 10.1007/s10593-014-1496-1

Franceschini, A. et al., 2013. STRING v9.1: Protein-Protein Interaction Networks, With Increased Coverage and Integration. Nucleic Acids Research, 41(1), pp.808-815. doi: 10.1093/nar/gks1094

Golonko, A. et al., 2019. Curcumin as Tyrosine Kinase Inhibitor in Cancer Treatment. European Journal of Medicinal Chemistry, 181(111512). pp.1-25. doi: 10.1016/j.ejmech.2019.07.015

Haddadi, N. et al., 2018. PTEN/PTENP1: 'Regulating the Regulator of RTK-Dependent PI3K/Akt Signalling', New Targets for Cancer Therapy. Molecular Cancer, 17(37), pp.1-14. doi: 10.1186/s12943-018-0803-3

Hamzehzadeh, L. et al., 2018. The Versatile Role of Curcumin in Cancer Prevention and Treatment: A Focus on PI3K/AKT Pathway. Journal of Cellular Physiology, 233(10), pp.6530-6537. doi: 10.1002/jcp.26620.

Ivanov, S.M. et al., 2018. ADVERPred-Web Service for Prediction of Adverse Effects of Drugs. Journal of Chemical Information and Modeling, 58(1), pp.8-11. doi: 10.1021/acs.jcim.7b00568.

Jadhav, P.B., Yadav, A.R. & Gore, M.G., 2015. Concept of Drug Likeness in Pharmaceutical Research. International Journal of Pharma and Bio Science, 6(4), pp.142-154.

Jamkhande, P. G. et al., 2014. Antioxidant, Antimicrobial Activity and In Silico PASS Prediction of Annona reticulata Linn. Root Extract. Beni-Suef University Journal of Basic and Applied Sciences, 3(2), pp.140-148. doi: 10.1016/j.bjbas.2014.05.008

Kilo, A.L. et al., 2019. Studi Potensi Pirazolin Tersubstitusi 1-N dari Tiosemikarbazon sebagai Agen Antiamuba Melalui Uji in Silico (Study of Potential of 1-N-Substituted Pyrazoline Analogues of Thiosemicarbazones as Antiamoebic Agent using In Silico Screening). Indonesia Journal of Chemical Research, 7(1), pp.9-16. doi: 10.30598//ijcr.2019.7-akr

Lazzeroni, M. et al., 2012. Oral low dose and topical tamoxifen for breast cancer prevention: modern approaches for an old drug. Breast Cancer Research, 14(5), 1–11. doi: 10.1186/bcr3233

Maduabuchi, E.K. & Awucha, N.E., 2020. Phytochemistry and GC-MS Analysis of Methanolic Leaf Extract of Newbouldia leavis (Bignonacea). Journal of Pharmacognosy and Phytochemistry, 9(2), pp. 1998-2004.

Mele, S. & Johnson, T.K., 2019. Receptor Tyrosine Kinases in Development: Insights from Drosophila. International Journal of Molecular Sciences, 21(188), pp.1-21. doi: 10.3390/ijms21010188

Moon, A. et al., 2017. Insilico Prediction of Toxicity of Ligands Utilizing Admetsar. International Journal of Pharma and Bio Sciences, 8(3), pp.674-677. doi: 10.22376/ijpbs.2017.8.3.b674-677

Nagahama, K. et al., 2016. Discovery of A New Function of Curcumin Which Enhances Its Anticancer Therapeutic Potency. Scientific Reports, 6(30962), pp.1-14. doi: 10.1038/srep30962

Nerkar, A.G. et al., 2012. In Silico Screening, Synthesis and Pharmacological Evaluation of Novel Quinazolinones as NMDA Receptor Inhibitors for Anticonvulsant Activity. International Journal of Pharmacy and Pharmaceutical Sciences, 4(3), pp.449-453.

Papadimitrakopoulou, V., 2012. Development of PI3K/AKT/mTOR Pathway Inhibitors and Their Application in Personalized Therapy for Non-Small-Cell Lung Cancer. Journal of Thorac Oncology, 7(8), pp.1315-1326. doi: 10.1097/JTO.0b013e31825493eb

Pramely, R. & Raj, T.L.S., 2012. Prediction of Biological Activity Spectra of A Few Phytoconstituents of Azadirachta indicia A. Juss. Journal of Biochemical Technology, 3(4), pp.375-379.

Puteri, F.D., 2020. Efek Kurkumin Pada Kunyit (Curcuma longa) Sebagai Pengobatan Kanker Lambung (Effect of Curcumin on Turmeric (Curcuma longa) as a Tretment for Stomach Cancer). Jurnal Ilmiah Kesehatan Sandi Husada, 9(2), pp.860-864. doi: 10.35816/jiskh.v10i2.426

Rahimi, N., 2017. Defenders and Challengers of Endothelial Barrier Function. Frontiers in Immunology, 8(1847), pp.1-10. doi: 10.3389/fimmu.2017.01847

Rawluk, J. & Waller, C.F., 2018. Gefitinib. Recent Results Cancer Research, 211, pp.235-246. doi: 10.1007/978-3-319-91442-8_16

Shi, X. et al., 2019. Research Progress on the PI3K/AKT Signaling Pathway in Gynecological Cancer (Review). Molecular Medicine Reports, 19(6), pp.4529-4535. doi: 10.3892/mmr.2019.10121

Syahputra, G, Ambarsari, L. & Sumaryada, T., 2014. Simulasi docking kurkumin enol, bisdemetoksikurkumin dan analognya sebagai inhibitor enzim12-lipoksigenase. Biofisika, 10(1), pp.55-67.

Tamaddoni, A. et al., 2020. The Anticancer Effects of Curcumin via Targeting the Mammalian Target of Rapamycin Complex 1 (mTORC1) Signaling Pathway. Pharmacological Research, 156(104798), pp.1-11. doi: 10.1016/j.phrs.2020.104798

Tomeh, M.A., Hadianamrei, R. & Zhao, X., 2019. A Review of Curcumin and Its Derivatives as Anticancer Agents. International Journal of Molecular Sciences, 20(1033), pp.1-26. doi: 10.3390/ijms20051033

Weni, M., Safithri, M. & Seno, D.S.H., 2020. Molecular Docking of Active Compounds Piper crocatum on The Alpha-Glucosidase Enzyme as Anticiabetic. Indonesian Journal of Pharmaceutical Science and Thechnology, 7(2), pp.64-72. doi: 10.24198/ijpst.v7i2.21120



DOI: https://doi.org/10.22146/jtbb.74905

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