Antiproliferative activity of hamigerone and radicinol isolated from Bipolaris papendorfii

Abstract

Secondary metabolites from fungi organisms have extensive past and present use in the treatment of many diseases and serve as compounds of interest both in their natural form and as templates for synthetic modification. Through high throughput screening (HTS) and bioassay-guided isolation, we isolated two bioactive compounds hamigerone (1) and radicinol (2). These compounds were isolated from fungus Bipolaris papendorfii, isolated from the rice fields of Dera, Himachal Pradesh, India. The structures of the compounds were established on the basis of spectroscopic data, namely, NMR ((1)H, (13)C, mass, and UV). Both compounds were found to be antiproliferative against different cancer cells. Furthermore we have also noted that both compounds showed increase in apoptosis by favorably modulating both tumor suppressor protein (p53) and antiapoptic protein (BCL-2), and in turn increase caspase-3 expression in cancer cells. This is the first report of these compounds from fungus Bipolaris papendorfii and their anticancer activity.

Figure 1

Phylogenetic analysis of the ITS region sequence obtained from sample PM0853873 in comparison with the nearest type strain sequences. The tree was constructed based on rRNA gene sequences (ITS region) using the Maximum Composite Likelihood Method.

Figure 2

Structures of hamigerone (1) and radicinol (2).

Figure 3

Elevation of p53 expression on treatment with hamigerone and radicinol in Panc-1 cells. The nucleus was stained with Hoechst 3342 (blue color), the expression of p53 protein levels was detected using Dylight 549 (red color), and the represented images are composite images of both channels. The quantitative data of p53 expression against untreated control cells is denoted as bar diagram. 1000 cells were counted for each replicate well and the results were presented as an average ± SE.

Figure 4

Decreased expression of BCL-2 levels on treatment with hamigerone and radicinol in Panc-1 cells. The nucleus was stained with Hoechst 3342 (blue color), the expression of BCL-2 protein levels was detected using Dylight 549 (red color), and the represented images are composite images of both channels. The quantitative data of BCL-2 expression against untreated control cells is represented as bar diagram. 1000 cells were counted for each replicate well and the results were presented as an average ± SE.

Figure 5

Induction of caspase 3 expression on treatment with hamigerone and radicinol in Panc-1 cells. The nucleus was stained with Hoechst 3342 (blue color), the expression of caspase 3 protein levels was detected using Dylight 549 (red color), and the represented images are composite images of both channels. The quantitative data of caspase 3 expression against control is showed as bar diagram. 1000 cells were counted for each replicate well and the results were presented as an average ± SE.