Research Article: Diaphorin, a polyketide produced by a bacterial symbiont of the Asian citrus psyllid, kills various human cancer cells

Date Published: June 10, 2019

Publisher: Public Library of Science

Author(s): Atsushi Nakabachi, Keiko Okamura, Richard Mankin.

http://doi.org/10.1371/journal.pone.0218190

Abstract

Diaphorin is a polyketide produced by Candidatus Profftella armatura (Betaproteobacteria), an organelle-like defensive symbiont harbored by a plant sap-sucking insect, Asian citrus psyllid Diaphorina citri (Hemiptera: Liviidae). Diaphorin belongs to the pederin family, a group of compounds that share much of their core structure with that of pederin, which is characterized by two dihydropyran rings bridged by an N-acyl aminal. Most members of this family have potent antitumor activity, making them promising anticancer drug candidates. The present study assessed the therapeutic potential of diaphorin for its antitumor activity against 39 human cancer cell lines including those from breast, brain, colon, lung, skin, ovary, kidney, stomach, and prostate. The results showed that diaphorin had inhibitory activity against all 39 cancer cell lines tested. The GI50, TGI, and LC50 values ranged from 0.28 μM– 2.4 μM, 1.6 μM –11 μM, and 7.5 μM–> 100 μM, respectively. These values are among the highest in the pederin family, indicating that the anticancer activity of diaphorin is milder than those of other pederin congeners. The inhibitory effects of diaphorin significantly differed among the distinct cancer types. The maximum difference was about 10-fold, which was similar to those of most other pederin congeners.

Partial Text

A variety of invertebrate animals harbor endosymbiotic microbes to deter natural enemies, which makes them among the richest sources of biologically active secondary metabolites [1–6]. Pederin family compounds, mostly isolated from marine sponges, are polyketides that share much of their core structure with that of pederin, which is characterized by two dihydropyran rings bridged by an N-acyl aminal [7–12]. Most compounds in this family, including pederin, mycalamides, onnamides, theopederins, and psymberin, exhibit potent antitumor activity, making them promising as anticancer drug candidates [7–10,13–20]. Mycalamide A not only inhibited replication of various cancer cells in vitro but also improved the survival of mice bearing ascitic lymphomas and a variety of other ascitic and solid tumors [15]. Moreover, this compound exhibited cancer preventive properties, inhibiting epidermal growth factor (EGF)-induced neoplastic transformation in murine cells [20]. Analysis using 60 human cancer cell lines revealed that psymberin, also known as irciniastatin A [21], has an remarkably selective activity toward solid tumor cells, making it one of the most promising lead drug candidates among a variety of other possible leads from different structural classes [22].

 

Source:

http://doi.org/10.1371/journal.pone.0218190