Bioinformatic Study of the Active Compound of Morusin in Mulberry (Morus alba) against Breast Cancer

Sarmoko Sarmoko, Afif Hariawan Pratama, Nur Amalia Choironi, Muhammad Salman Fareza


Morusin, an active constituent of the mulberry plant (Morus alba), exhibits inhibitory effects on several types of cancer cells in vitro, including breast cancer. This study aimed to identify potential target proteins of morusin, investigate the binding energy, and explore type of interactions between morusin and the target protein. Morusin target was searched using the PubMed, STITCH, STRING, and Cytoscape databases. Subsequently, the obtained morusin target protein data underwent processing using Autodock Tools and DS BIOVIA to facilate the simulation of molecular docking between morusin and the target protein. The study identified EGFR, SRC, and MAPK1 as potential targets for morusin. Docking simulations revealed that both EGFR and SRC represent viable targets for morusin, as their binding energies were lower than those of the native ligand and lapatinib. Specifically, the bond energies at EGFR were -9.6, -7.5, and -9.2 kcal/mol for morusin, the native ligand, and lapatinib, respectively. Similarly, at SRC, the corresponding bond energies were -8.2, -6.4, and -5.3 kcal/mol. Morusin demonstrated binding interactions with Leu694, Val702, Leu820, Ala719, Leu768, and Lys721 at the active site of EGFR, and with Lys295 and Gly344 at the binding active sites of SRC. Consequently, morusin has the potential to suppress cancer cell growth by targeting EGFR and SRC.

Keywords: cancer cells, EGFR and SRC as targets, molecular docking, morusin, mulberry plant.

Full Text:



Aronov, A.M., Baker, C., Bemis, G.W., Cao, J., Chen, G., Ford, P.J., et al., 2007, Flipped out: structure-guided design of selective pyrazolylpyrrole ERK inhibitors, J. Med. Chem., 50(6), 1280–1287. CrossRef

Braicu, C., Buse, M., Busuioc, C., Drula, R., Gulei, D., Raduly, L., et al., 2019, A comprehensive review on MAPK: A promising therapeutic target in cancer, Cancers (Basel), 11(10), 1618. CrossRef

Chen, C.-P., Chan, K.-C., Ho, H.-H., Huang, H.-P., Hsu, L.-S., and Wang, C.-J., 2022, Mulberry polyphenol extracts attenuated senescence through inhibition of Ras/ERK via promoting Ras degradation in VSMC, Int J Med Sci., 19(1), 89–97. CrossRef

Dalgarno, D., Stehle, T., Narula, S., Schelling, P., van Schravendijk, M.R., Adams, S., et al., 2006, Structural basis of Src tyrosine kinase inhibition with a new class of potent and selective trisubstituted purine-based compounds, Chem Biol Drug Des., 67, 46–57. CrossRef

Gautama, W., 2022, Breast cancer in indonesia in 2022: 30 years of marching in place, Indonesian Journal of Cancer, 16(1). 1-2. CrossRef

Giridharan, S., and Srinivasan, M., 2018, Mechanisms of NF-κB p65 and strategies for therapeutic manipulation, J Inflamm Res., 11, 407–419. CrossRef

Goel, S., DeCristo, M.J., Watt, A.C., BrinJones, H., Sceneay, J., Li, B.B., et al., 2017, CDK4/6 inhibition triggers anti-tumour immunity, Nature, 548(7668), 471–475. CrossRef

Hajalsiddig, T.T.H., Osman, A.B.M., and Saeed, A.E.M., 2020, 2D-QSAR Modeling and Molecular Docking Studies on 1H-Pyrazole-1-carbothioamide Derivatives as EGFR Kinase Inhibitors, ACS Omega, 5, 18662–18674. CrossRef

Hermawan, A., Ikawati, M., Jenie, R.I., Khumaira, A., Putri, H., Nurhayati, I.P., et al., 2021, Identification of potential therapeutic target of naringenin in breast cancer stem cells inhibition by bioinformatics and in vitro studies, Saudi Pharm J., 29(1), 12–26. CrossRef

Hurtado, D.X., Castellanos, F.A., Coy-Barrera, E., and Tello, E., 2020, Prostaglandins Isolated from the Octocoral Plexaura homomalla: In Silico and In Vitro Studies Against Different Enzymes of Cancer, Mar Drugs, 18(3), 141. CrossRef

Kang, S., Kim, E.-O., Kim, S.-H., Lee, J.-H., Ahn, K.S., Yun, M., and Lee, S.-G., 2017, Morusin induces apoptosis by regulating expression of Bax and Survivin in human breast cancer cells, Oncol. Lett., 13(6), 4558–4562. CrossRef

Kufareva, I., and Abagyan, R., 2008, Type-II kinase inhibitor docking, screening, and profiling using modified structures of active kinase states, J. Med. Chem., 51(24), 7921–7932. CrossRef

Lallo, S., Hardianti, B., Umar, H., Trisurani, W., Wahyuni, A., and Latifah, M., 2020, Anti-inflammatory and Wound Healing Activities of Mulberry Barks (Morus alba L.) Extract, Galenika Journal of Pharmacy, 6(1), 26–36. CrossRef

Lee, H., Jeong, A.J., and Ye, S.-K., 2019, Highlighted STAT3 as a potential drug target for cancer therapy, BMB Rep., 52(7), 415–423. CrossRef

Muhammad, N., Bhattacharya, S., Steele, R., Phillips, N., and Ray, R.B., 2017, Involvement of c-Fos in the Promotion of Cancer Stem-like Cell Properties in Head and Neck Squamous Cell Carcinoma, Clin. Cancer Res., 23(12), 3120–3128. CrossRef

Ortiz, M.A., Mikhailova, T., Li, X., Porter, B.A., Bah, A., and Kotula, L., 2021, Src family kinases, adaptor proteins and the actin cytoskeleton in epithelial-to-mesenchymal transition, Cell Commun. Signal., 19(1), 67. CrossRef

Panek-Krzyśko, A., and Stompor-Gorący, M., 2021, The Pro-Health Benefits of Morusin Administration-An Update Review, Nutrients, 13(9), 3043. CrossRef

Park, J.H., Liu, Y., Lemmon, M.A., and Radhakrishnan, R., 2012, Erlotinib binds both inactive and active conformations of the EGFR tyrosine kinase domain, Biochem. J., 448(3), 417–423. CrossRef

Rong, B., and Yang, S., 2018, Molecular mechanism and targeted therapy of Hsp90 involved in lung cancer: New discoveries and developments (Review), Int. J. Oncol., 52(2), 321–336. CrossRef

Shirai, Y., Chow, C.C.T., Kambe, G., Suwa, T., Kobayashi, M., Takahashi, I., et al., 2021, An Overview of the Recent Development of Anticancer Agents Targeting the HIF-1 Transcription Factor, Cancers (Basel), 13(11), 2813. CrossRef

Subramaniyan, V., Fuloria, S., Gupta, G., Kumar, D.H., Sekar, M., Sathasivam, K.V., et al., 2022, A review on epidermal growth factor receptor’s role in breast and non-small cell lung cancer, Chem. Biol. Interact., 351, 109735. CrossRef

Sun, Y., and Yang, J., 2019, A bioinformatics investigation into the pharmacological mechanisms of the effect of Fufang Danshen on pain based on methodologies of network pharmacology, Sci. Rep., 9, 5913. CrossRef

Tang, J.-W., Xiong, X.-S., Qian, C.-L., Liu, Q.-H., Wen, P.-B., Shi, X.-Y., et al., 2021, Network pharmacological analysis of ethanol extract of Morus alba linne in the treatment of type 2 diabetes mellitus, Arabian Journal of Chemistry, 14(10), 103384. CrossRef

Wani, M.Y., Ganie, N.A., Wani, D.M., Wani, A.W., Dar, S.Q., Khan, A.H., et al., 2023, The phenolic components extracted from mulberry fruits as bioactive compounds against cancer: A review, Phytother Res., 37(3), 1136–1152. CrossRef

Zhang, X., Shen, T., Zhou, X., Tang, X., Gao, R., Xu, L., et al., 2020, Network pharmacology based virtual screening of active constituents of Prunella vulgaris L. and the molecular mechanism against breast cancer, Sci. Rep., 10, 15730. CrossRef


Copyright (c) 2023 Sarmoko Sarmoko, Afif Hariawan Pratama, Nur Amalia Choironi, Muhammad Salman Fareza

Indexed by:




Indonesian Society for Cancer Chemoprevention