Background: Periplocin is used for treatment of rheumatoid arthritis, reinforcement of bones and tendons, palpitations or shortness of breath and lower extremity edema in traditional medicine. Our previous findings suggested that periplocin could inhibit the growth of lung cancer both in vitro and in vivo. But the biological processes and molecular pathways by which periplocin induces these beneficial effects remain largely undefined.
Methods: To explore the molecular mechanisms of periplocin involved in anti-cancer activity, in the present study the protein profile changes of human lung cancer cell lines A549 in response to periplocin treatment were investigated using the proteomics approaches (2-DE combined with MS/MS). Western blot was employed to verify the changed proteins. Interactions between changed proteins were analyzed by STRING.
Results: 29 down-regulated protein species named GTP-binding nuclear protein Ran (RAN), Rho GDP-dissociation inhibitor 1 (ARHGDIA), eukaryotic translation initiation factor 5A-1 (EIF5A) and Profilin-1(PFN1), and 10 up-regulated protein species named Heat shock cognate 71 kDa protein (HSPA8),10 kDa heat shock protein (HSPE1), and Cofilin-1(CFL-1) were identified. Among them, GTP-binding nuclear protein Ran (RAN) and Rho GDP-dissociation inhibitor 1 (ARHGDIA) were the most significantly changed (over tenfold). The proteasome subunit beta type-6 (PSMB6), ATP synthase ecto-α-subunit (ATP5A1), Aldehyde dehydrogenase 1 (ALDH1) and EIF5A were verified by immunoblot assays to be dramatically down-regulated. By STRING bioinformatics analysis revealing interactions and signaling networks it became apparent that the proteins changed they are primarily involved in transcription and proteolysis.
Conclusion: Periplocin inhibited growth of lung cancer by down-regulating proteins, such as ATP5A1, EIF5A, ALDH1 and PSMB6. These findings may improve our understanding of the molecular mechanisms underlying the anti-cancer effects of periplocin on lung cancer cells.
© 2014 S. Karger AG, Basel.