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

Document Type : Research Articles

Authors

1 Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia.

2 Macromolecular Engineering Laboratory, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada, Sekip Utara, Yogyakarta, Indonesia.

3 Medicinal Chemistry Laboratory, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada, Sekip Utara, Yogyakarta, Indonesia.

4 Laboratory of Tumor Cell Biology, Nara Institute of Science and Technology, Ikoma, Nara, Japan.

Abstract

Objective: 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. Methods: 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. Results: 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. Conclusion: Our preliminary study collectively reinforces the potential effect of CCA-1.1 through the inhibition of highly aggressive cell migration, particularly in breast cancer.

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Volume 22, Issue 6
June 2021
Pages 1827-1836
  • Receive Date: 01 February 2021
  • Revise Date: 17 May 2021
  • Accept Date: 17 June 2021
  • First Publish Date: 17 June 2021