In vitro and in silico studies of anticancer activities of pectic acid and pectin oligosaccharide in Epstein-Barr virus-positive nasopharyngeal carcinoma.

Pectic acid (polygalacturonic acid, PGA) and pectin oligosaccharides (POS) have shown selective anticancer activities with cytotoxicity against various cancer cells, including breast adenocarcinoma MCF-7. While promising, their anticancer activities against the nasopharyngeal carcinoma (NPC) have yet to be determined. To this end, the antiproliferation activities of pectic acid and enzymatically derived unsaturated POS trimer were investigated against the EBV-positive NPC cell line, C666-1, as well as on MCF-7 (as positive control) and NIH-3T3 cells (as non-tumorigenic cell model). Our study shows that both POS trimer and PGA can inhibit C666-1 cells' proliferation at concentrations above 20 mg/mL and 2.5 mg/mL, respectively. Previous studies had also demonstrated that one of the key biological targets for these compounds is the human galectin-3 (hGal3). However, the binding mode of pectic acid and the unsaturated POS trimer to human galectin-3 is still lacking. To investigate this, in silico molecular docking and all-atom molecular dynamics simulations were performed. Analysis of the MD trajectories revealed that the unsaturated POS trimer prefers binding to hGal3 oligomer over hGal3 monomer with a ligand: protein monomer ratio of 1:2 and 1:3. On the other hand, both hGal3 monomer and dimer were found to bind stably to the POS 15-mer (as PGA model) along its linear chain throughout the simulation. In conclusion, both unsaturated POS trimer and PGA have the potential to be novel anticancer agents against EBV-positive NPC, though further development to increase their potency and/or selectivity would be necessary.