Mining Natural Products with Anticancer Biological Activity through a Systems Biology Approach

Abstract

Natural products, like turmeric, are considered powerful antioxidants which exhibit tumor-inhibiting activity and chemoradioprotective properties. Nowadays, there is a great demand for developing novel, affordable, efficacious, and effective anticancer drugs from natural resources. In the present study, we have employed a stringent in silico methodology to mine and finally propose a number of natural products, retrieved from the biomedical literature. Our main target was the systematic search of anticancer products as anticancer agents compatible to the human organism for future use. In this case and due to the great plethora of such products, we have followed stringent bioinformatics methodologies. Our results taken together suggest that natural products of a great diverse may exert cytotoxic effects in a maximum of the studied cancer cell lines. These natural compounds and active ingredients could possibly be combined to exert potential chemopreventive effects. Furthermore, in order to substantiate our findings and their application potency at a systems biology level, we have developed a representative, user-friendly, publicly accessible biodatabase, NaturaProDB, containing the retrieved natural resources, their active ingredients/fractional mixtures, the types of cancers that they affect, and the corresponding experimentally verified target genes.

Figure 1

Bar graph depicting the distribution of natural products (orange) and genes (blue) with respect to cancer types.

Figure 2

STRING output functional network of the 81 genes/gene products. The nodes represent molecules and the connecting lines (edges) indicate an interaction confidence score above 0.9.

Figure 3

Bar plot depicting the overrepresented cancer-related pathways across target genes.

Figure 4

Bipartite network displaying TCGA-derived cancer-gene associations. The interactions are presented in a circular mode; the cancer types are shown at the center and the genes at the periphery. The size of the nodes is proportional to their connectivity degree.

Figure 5

NaturaProDB workflow showing the (a) example input query, (b) example results page, and (c) “Natural Products Network,” where the node size is proportional to their connectivity degree.