CCA-1.1, a Novel Curcumin Analog, Exerts Cytotoxic anti- Migratory Activity toward TNBC and HER2-Enriched Breast Cancer Cells

• DOI: 10.31557/apjcp.2021.22.6.1827
• Publication Date: 2021-06-28T16:34:29Z
• Authors: Dhania Novitasari; Riris Jenie; Rohmad Utomo; Jun ya Kato; Edy Meiyanto
• Keywords: Curcumin; Receptor, ErbB-2; Antineoplastic Agents; Drug Synergism; Triple Negative Breast Neoplasms; Chemoprevention; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Cell Movement; Doxorubicin; Drug Resistance, Neoplasm; Tumor Cells, Cultured; Humans; Original Article; Female; Cell Proliferation

Chemoprevention curcumin Analog-1.1 (CCA-1.1) demonstrates antineoplastic effect toward cancer cells. By using triple-negative breast cancer (TNBC), 4T1, and human epidermal growth factor receptor 2 (HER2)-enriched metastatic cells (MCF-7/HER2), we evaluate the cytotoxic and antimigration activities from CCA-1.1.The cytotoxic activities from a single treatment of CCA-1.1 and in combination with doxorubicin were determined through MTT assay. We also calculated the selectivity index and combination index of CCA-1.1 from the cytotoxic data. Migrating cells were evaluated using wound healing assay, and the MMP2 and MMP9 secretion levels were determined through gelatin zymography.As hypothesized, CCA-1.1 performed cytotoxic activity during treatment in 4T1 and MCF-7/HER2 cancer cells with good selectivity (Selectivity Index >2). In addition, CCA-1.1 demonstrated a synergistic effect in combinatorial treatment with a low dose of doxorubicin. A single treatment of CCA-1.1 repressed cell migration in 4T1 and MCF-7/HER2 cells. Under gelatin zymography, CCA-1.1 subsided the activities of MMP-9, thereby revealing the potency of CCA-1.1 as an anti-migratory agent. Moreover, MMP-9 was also eminently expressed in TNBC and HER2-enriched breast cancer cells when compared with that in other subtypes.Our preliminary study collectively reinforces the potential effect of CCA-1.1 through the inhibition of highly aggressive cell migration, particularly in breast cancer.