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.
Highlights
In the recent years, considerable numbers of cuttingedge studies have been performed using transcriptomic and proteomic technologies to investigate specific oncological pathways that has escalated the development of new drug targets (Armando et al, 2020)
We assessed the single treatment of CCA-1.1 against 4T1 and MCF-7/human epidermal growth factor receptor 2 (HER2) cells (Figure 2A and 2B) that demonstrated the cytotoxic activity with IC50 values after 24 and 48 h of treatment (Table 1)
The present study aimed to determine a novel candidate as an anticancer agent with multiple targets in the cancer pathway that can overcome the limitations during therapy (Wang et al, 2019)
Summary
Considerable numbers of cuttingedge studies have been performed using transcriptomic and proteomic technologies to investigate specific oncological pathways that has escalated the development of new drug targets (Armando et al, 2020). CCA-1.1 generated intracellular ROS, which resulted in cell senescence and cell cycle arrest in colorectal cancer cells (Wulandari et al, 2020c), and the possible target was documented through a bioinformatics approach (Wulandari et al, 2020a). CCA-1.1 performed better than PGV-1 in a molecular docking study, suggesting a higher binding affinity toward several ROS scavengers (Utomo et al, 2021). These reported data demonstrated the impressive results of CCA-1.1 for the further elucidation of its molecular mechanism in different approaches against cancer cells
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