Three compounds from banana pseudostem inhibit mitotic cell division by interacting with tubulin and cyclin-dependent kinase 2 proteins: in vivo, in vitro and in silico approach

To identify putative antimitotic compounds, the pseudostem of banana plant (PSBP) was chosen and assays were carried out with aqueous extract of PSBP. Aqueous extract of PSBP decreased the mitotic index in onion root tips. Moreover, this extract inhibited the regeneration of blastema in amputated earthworms. Validation of this extract with MTT (3-(4, 5-dimethyl thiazolyl-2-yl)—2, 5-diphenyltetrazolium bromide) assay using MCF-7 human breast cancer cell line confirmed the presence of antimitotic activity. LC–MS analysis of this extract revealed the presence of three potential antimitotic compounds viz. α-tocotrienoxyl radical (ATT), 1,2,4-nonadecanetriol (NAT), and 3′,4′,7-trihydroxyisoflavone (THIF). Molecular docking studies suggested that these three compounds associate with α- and β-tubulin of mammalian cells and might have influenced the polymerization of microtubules. Besides, these compounds bind with active sites of cyclin-dependent kinase 2 (CDK2) protein which is required for cell division. Molecular dynamics (MD) simulation studies indicated the strong binding of THIF with α-tubulin, whereas ATT and NAT ligands with CDK2 protein. Our results clearly indicated the presence of three different antimitotic compounds from new resource and inhibit mitotic cell division. Pseudostem of banana plants could be an excellent resource for production of commercially significant antimitotic compounds.