Antiproliferative Potential of Gloriosine: A Lead for Anticancer Drug Development

Abstract

Gloriosine, a colchicine-like natural product, is widely obtained from Gloriosa superba roots. Despite having remarkable anticancer potential, colchicine could not pave its way to the clinic, while gloriosine is yet to be investigated for its pharmacological effects. In the present work, 14 compounds, including gloriosine, were isolated from the G. superba roots and were characterized by NMR spectroscopy. Gloriosine (11) was evaluated for its antiproliferative activity against a panel of 15 human cancer cell lines of different tissues and normal breast cells. Gloroisine (11) displayed significant antiproliferative activity against various cancer cell lines selectively, with IC₅₀ values ranging from 32.61 to 100.28 nM. Further, gloriosine (11) was investigated for its apoptosis-inducing ability and found to form apoptotic bodies. It also inhibited A549 cell migration in the wound healing assay. Finally, molecular docking studies were performed to explore the possible binding modes of gloriosine with the colchicine-binding site of tubulin protein. Our findings suggested that gloriosine might be a potential lead for anticancer drug discovery.

Figure 1

Pharmacophoric features of colchicine as colchicine-binding site (CBS) inhibitors. The red and pink points are hydrogen bond acceptors, the blue point and brown lines represent hydrophobic centers, and the green lines represent the planar group.

Figure 2

Chemical structures of compounds (1–14) isolated from the G. superba roots.

Figure 3

Nuclear staining after treatment with different concentrations (50, 100, and 500 nM) of gloriosine (11) and 500 nM of colchicine (10) on A549 cells for 24 h revealed the formation of apoptotic bodies in a dose-dependent manner.

Figure 4

(a) Effect of gloriosine (11) and colchicine (10) on in vitro cell migration in A549 cells after 24 h. (b) Gloriosine (11) inhibited A549 cells migration in a dose-dependent manner.

Figure 5

Protein–ligand interaction diagram of compounds (A) gloriosine and (B) colchicine against the colchicine-binding site of tubulin protein (PDB ID: 4O2B).

Figure 6

MD simulation of gloriosine complexed with tubulin. (A) RMSD plot of tubulin and gloriosine. (B) Root-mean-square fluctuation (RMSF) plot of tubulin. (C) Protein–ligand contacts between tubulin and gloriosine during a MD run. (D) Interactions of gloriosine with tubulin during a MD run.