Network Pharmacological Analysis Identifies the Curcumin Analog CCA-1.1 Targeting Mitosis Regulatory Process in HER2-Positive Breast Cancer
Keywords:
CCA-1.1, Bioinformatics, Mitosis, HER2-amplified breast cancer
Abstract
Recent studies present that the CCA-1.1 (a curcumin derivative) impedes the proliferation of breast cancer cells (luminal, HER2-overexpressed, and TNBC cells). Currently, we analyze the possible target of action of CCA-1.1, particularly in breast cancer cells with HER2 amplification using bioinformatics analysis. The differentially expressed genes (DEGs) of HER2-positive breast cancer were retrieved from TCGA-BRCA data (via UALCAN). We used three web-based tools (Swiss Target Prediction, BindingDB, and TargetNet) to predict the potential target of CCA-1.1 using the SMILE-similarity feature. The functional annotation and network enrichment were processed in WebGestalt. The alteration of selected genes was observed in CBioPortal. The protein-protein interaction (PPI) network was constructed in STRING, then ranked based on the degree score using Cytohubba feature in Cytoscape. The survival analysis from the hub-gene was collected in GEPIA2 with selection only for HER2-positive breast cancer cases. The correlation between the hub genes and tumor-infiltrating immune markers was determined using TIMER web tools. The pathway network analysis highlighted the cell cycle regulation in mitosis as affected signaling amid the putative CCA-1.1 targets. We denoted eight potential genes that could be responsible for inhibiting mitosis regulation upon CCA-1.1 treatment, including AURKA, AURKB, PLK1, TPX2, KIF11, MELK, CDK1, and CHEK1. Several of the potential markers (AURKB, AURKA, CDK1, and CHEK1) revealed to be correlated with the immune cells’ infiltration markers. CCA-1.1 might regulate mitosis to induce cell cycle arrest and lead to cell death. The predicted targets of CCA-1.11 gave insight into the potency of CCA-1.1 to be with immunotherapy. Further validation of the data presented in the study is essentially needed to develop CCA-1.1 for breast cancer.
References
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Joukov, V., & Nicolo, A. D. (2018). Aurora-PLK1 cascades as key signaling modules in the regulation of mitosis. Science Signaling, 11(543). https://doi.org/10.1126/scisignal.aar4195
Kaushik, A. C., Mehmood, A., Dai, X., & Wei, D.-Q. (2020). A comparative chemogenic analysis for predicting Drug-Target Pair via Machine Learning Approaches. Scientific Reports, 10(1), 6870. https://doi.org/10.1038/s41598-020-63842-7
Kishimoto, T. (2015). Entry into mitosis: A solution to the decades-long enigma of MPF. Chromosoma, 124(4), 417–428. https://doi.org/10.1007/s00412-015-0508-y
Krenn, V., & Musacchio, A. (2015). The Aurora B Kinase in Chromosome Bi-Orientation and Spindle Checkpoint Signaling. Frontiers in Oncology, 5, 225. https://doi.org/10.3389/fonc.2015.00225
Lai, H.-W., Chien, S.-Y., Kuo, S.-J., Tseng, L.-M., Lin, H.-Y., Chi, C.-W., & Chen, D.-R. (2011). The Potential Utility of Curcumin in the Treatment of HER-2-Overexpressed Breast Cancer: An In Vitro and In Vivo Comparison Study with Herceptin. Evidence-Based Complementary and Alternative Medicine, 2012, e486568. https://doi.org/10.1155/2012/486568
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Lee, K., & Rhee, K. (2011). PLK1 phosphorylation of pericentrin initiates centrosome maturation at the onset of mitosis. The Journal of Cell Biology, 195(7), 1093–1101. https://doi.org/10.1083/jcb.201106093
Lee, M., Rivera-Rivera, Y., Moreno, C. S., & Saavedra, H. I. (2017). The E2F activators control multiple mitotic regulators and maintain genomic integrity through Sgo1 and BubR1. Oncotarget, 8(44), 77649–77672. https://doi.org/10.18632/oncotarget.20765
Lestari, B., Nakamae, I., Yoneda-Kato, N., Morimoto, T., Kanaya, S., Yokoyama, T., Shionyu, M., Shirai, T., Meiyanto, E., & Kato, J. (2019). Pentagamavunon-1 (PGV-1) inhibits ROS metabolic enzymes and suppresses tumor cell growth by inducing M phase (prometaphase) arrest and cell senescence. Scientific Reports, 9(1), 1–12. https://doi.org/10.1038/s41598-019-51244-3
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Liao, Y., Wang, J., Jaehnig, E. J., Shi, Z., & Zhang, B. (2019). WebGestalt 2019: Gene set analysis toolkit with revamped UIs and APIs. Nucleic Acids Research, 47(W1), W199–W205. https://doi.org/10.1093/nar/gkz401
Liberzon, A., Birger, C., Thorvaldsdóttir, H., Ghandi, M., Mesirov, J. P., & Tamayo, P. (2015). The Molecular Signatures Database (MSigDB) hallmark gene set collection. Cell Systems, 1(6), 417–425. https://doi.org/10.1016/j.cels.2015.12.004
Lindqvist, A., Rodríguez-Bravo, V., & Medema, R. H. (2009). The decision to enter mitosis: Feedback and redundancy in the mitotic entry network. The Journal of Cell Biology, 185(2), 193–202. https://doi.org/10.1083/jcb.200812045
Liu, H.-T., & Ho, Y.-S. (2018). Anticancer effect of curcumin on breast cancer and stem cells. Food Science and Human Wellness, 7(2), 134–137. https://doi.org/10.1016/j.fshw.2018.06.001
Lukas, C., Sørensen, C. S., Kramer, E., Santoni-Rugiu, E., Lindeneg, C., Peters, J. M., Bartek, J., & Lukas, J. (1999). Accumulation of cyclin B1 requires E2F and cyclin-A-dependent rearrangement of the anaphase-promoting complex. Nature, 401(6755), 815–818. https://doi.org/10.1038/44611
Meiyanto, E., Husnaa, U., Kastian, R. F., Putri, H., Larasati, Y. A., Khumaira, A., Pamungkas, D. D. P., Jenie, R. I., Kawaichi, M., Lestari, B., Yokoyama, T., & Kato, J. (2021). The Target Differences of Anti-Tumorigenesis Potential of Curcumin and its Analogues Against HER-2 Positive and Triple-Negative Breast Cancer Cells. Advanced Pharmaceutical Bulletin, 11(1), 188–196. https://doi.org/10.34172/apb.2021.020
Mimura, K., Ando, T., Poschke, I., Mougiakakos, D., Johansson, C. C., Ichikawa, J., Okita, R., Nishimura, M. I., Handke, D., Krug, N., Choudhury, A., Seliger, B., & Kiessling, R. (2011). T cell recognition of HLA-A2 restricted tumor antigens is impaired by the oncogene HER2. International Journal of Cancer, 128(2), 390–401. https://doi.org/10.1002/ijc.25613
Novitasari, D., Jenie, R. I., Utomo, R. Y., Kato, J. Y., & Meiyanto, E. (2021). CCA-1.1, a Novel Curcumin Analog, Exerts Cytotoxic anti- Migratory Activity toward TNBC and HER2-Enriched Breast Cancer Cells. Asian Pacific Journal of Cancer Prevention: APJCP, 22(6), 1827–1836. https://doi.org/10.31557/APJCP.2021.22.6.1827
Novitasari, D., Jenie, R. I., Wulandari, F., Putri, D. D. P., Kato, J., & Meiyanto, E. (2021). A Curcumin Like Structure (CCA-1.1) Induces Permanent Mitotic Arrest (Senescence) on Triple Negative Breast Cancer (TNBC) Cells, 4T1. Research Journal of Pharmacy and Technology, 14(8), 4375–4382. https://doi.org/10.52711/0974-360X.2021.00760
Novitasari, D., Wulandari, F., Jenie, R. I., Utomo, R. Y., Kato, J.-Y., & Meiyanto, E. (2021). A new curcumin analog, CCA-1.1, induces cell cycle arrest and senescence toward ER-positive breast cancer cells. International Journal of Pharmaceutical Research, 13(1), 1–9.
Peart, M. J., Poyurovsky, M. V., Kass, E. M., Urist, M., Verschuren, E. W., Summers, M. K., Jackson, P. K., & Prives, C. (2010). APC/C(Cdc20) targets E2F1 for degradation in prometaphase. Cell Cycle (Georgetown, Tex.), 9(19), 3956–3964. https://doi.org/10.4161/cc.9.19.13162
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Published
2022-12-07
How to Cite
Novitasari, D., Jenie, R. I., Kato, J.- ya, & Meiyanto, E. (2022). Network Pharmacological Analysis Identifies the Curcumin Analog CCA-1.1 Targeting Mitosis Regulatory Process in HER2-Positive Breast Cancer. Indonesian Journal of Pharmacy, 34(1), 54-64. https://doi.org/10.22146/ijp.4453
Issue
Section
Research Article
