Antitumor and antimitotic activity of aminochalcones in human cancer cells with differential P-glycoprotein expression

Background: Cancer remains a leading cause of mortality, with drug resistance, particularly mediated by P-glycoprotein (P-gp), limiting therapeutic efficacy [1]. Chalcones have emerged as promising anticancer agents due to their ability to inhibit tubulin polymerization and disrupt microtubule dynamics [2]. In this context, dual‑targeting strategies combining antimitotic activity with P‑gp inhibition, including chalcone‑based derivatives, have recently been reported as a means to overcome multidrug resistance [3]. Objective: This study aimed to evaluate the antitumor and antimitotic activity of eight aminochalcone derivatives in human cancer cell lines of diverse origins: melanoma (A375-C5), breast adenocarcinoma (MCF-7), non-small cell lung carcinoma (NCI-H460), ovarian carcinoma with dual resistance to paclitaxel and carboplatin (OVCAR8 PTX/CBP-R), and colon adenocarcinoma (HCT-15), each exhibiting different levels of P-glycoprotein expression, with HCT-15 as a well-established model for multidrug resistance studies. Methods: The antitumor activity of all compounds was assessed in five cancer cell lines using the sulforhodamine B assay to determine the GI50 values at 48 h (defined as the concentration required to inhibit 50% of cell growth), with doxorubicin as a control. Selectivity indices were calculated using the non-cancerous breast MCF10A cell line. Antimitotic activity was evaluated by phase-contrast microscopy and DAPI staining. Results: Seven of the eight compounds demonstrated potent cytotoxic activity across all tested cancer cell lines. The strongest selectivity was observed in HCT-15 cells, which highly express P-gp. All compounds exhibited antimitotic activity, although the extent varied among derivatives. Conclusions: These findings support the potential of aminochalcone derivatives as antimitotic and anticancer agents, particularly for targeting P-gp-mediated drug-resistant cancer cells.