Notwithstanding the advances in molecular target-based drugs,
chemotherapy remains the most common
cancer treatment, despite its high toxicity. Consequently, effective anticancer
therapies with fewer adverse effects are needed. Therefore, this study aimed to determine the anticancer activity of the
dichloromethane fraction (DCMF) isolated from Arrabidae brachypoda roots, whose components are three unusual dimeric
flavonoids. The toxicity of DCMF was investigated in breast (MCF-7), prostate (DU145), and cervical (HeLa)
tumor cells, as well as non-
tumor cells (PNT2), using
sulforhodamine B (cell viability), Comet (genotoxicity), clonogenicity (reproductive capacity) and wound healing (cell migration) assays, and atomic force microscopy (AFM) for ultrastructural cell membrane alterations. Molecular docking revealed affinity between
albumin and each rare
flavonoid, supporting the impact of
fetal bovine serum in DCMF antitumor activity. The IC50 values for MCF7, HeLa, and DU145 were 2.77, 2.46, and 2.51 µg/mL, respectively, and 4.08 µg/mL for PNT2. DCFM was not genotoxic to
tumor or normal cells when exposed to twice the IC50 for up to 24 h, but it inhibited
tumor cell migration and reproduction compared to normal cells. Additionally, AFM revealed alterations in the ultrastructure of
tumor nuclear membrane surfaces, with a positive correlation between DCMF concentration and
tumor cell roughness. Finally, we found a negative correlation between roughness and the ability of DCMF-treated
tumor cells to migrate and form colonies with more than 50 cells. These findings suggest that DCFM acts by causing ultrastructural changes in
tumor cell membranes while having fewer toxicological effects on normal cells.