Network Pharmacological Analysis Identifies the Curcumin Analog CCA-1.1 Targeting Mitosis Regulatory Process in HER2-Positive Breast Cancer

  • Dhania Novitasari 1. Doctoral Student of Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, 55281, Indonesia. 2. Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, 55281, Indonesia
  • Riris Istighfari Jenie 2. Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, 55281, Indonesia. 3. Laboratory of Macromolecular Engineering, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada, Sekip Utara, Yogyakarta, 55281, Indonesia
  • Jun-ya Kato 4. Laboratory of Tumor Cell Biology, Nara Institute of Science and Technology, Ikoma, Nara, 630-0192, Japan
  • Edy Meiyanto Professor of Pharmaceutical chemistry, Faculty of Pharmacy. Universitas Gadjah Mada
Keywords: CCA-1.1, Bioinformatics, Mitosis, HER2-amplified breast cancer


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.


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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).
Research Article

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