BONDUCELLIN SUPPRESSES COLORECTAL CANCER CELL PROLIFERATION AND STEMNESS THROUGH METHYLTRANSFERASE-LIKE 3

Abstract

Colorectal cancer (CRC) remains one of the most prevalent and lethal malignancies worldwide, necessitating the development of novel therapeutic strategies. Bonducellin, a naturally occurring flavonoid derived from Caesalpinia bonducella, has demonstrated promising anticancer properties. However, its molecular mechanism of action in CRC remains poorly understood. In this study, we investigated the potential of Bonducellin as an inhibitor of methyltransferase like 3 (METTL3), a key RNA methyltransferase implicated in CRC progression. Computational analyses, including molecular docking and molecular dynamics simulations, revealed a strong binding affinity of Bonducellin toward the S adenosylmethionine (SAM)-binding pocket of METTL3, stabilized by hydrogen bonding and hydrophobic interactions. Conceptual density functional theory (C-DFT) further supported the favorable electronic stability and reactivity profile of the molecule. In vitro assays demonstrated that Bonducellin significantly inhibited proliferation colon cancer cell line HCT116, with an IC₅₀ value of 45 µM. In addition, Bonducellin inhibited the colony formation, and migration of HCT116 cells. Acridine orange/ethidium bromide staining confirmed apoptosis induction, while immunofluorescence analysis revealed downregulation of METTL3 expression following treatment. These findings demonstrate that Bonducellin suppresses CRC cell growth and migration through METTL3 inhibition and apoptosis induction, highlighting its potential as a natural small-molecule lead for CRC therapy.