Comparative Proteomic Analysis of Anti-Cancer Mechanism by Periplocin Treatment in Lung Cancer Cells

Abstract

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.

Proteomics analysis of malignant and benign prostate tissue by 2D DIGE/MS reveals new insights into proteins involved in prostate cancer

“…The proteasome subunit, beta type, 6 (PSMB6) is part of 20S catalytic core of the proteasome that controls the cell cycle and other processes through the degradation of critical regulatory components and transcription factors . PSMB6 was found up regulated in hypoxia , lung cancer , and anaplastic thyroid cancers . The study of PSMB6 expression in prostate cancer was needed as this protein has been previously associated with the disease in only two studies with contradictory findings.…”

A validated LC–MS/MS assay for the simultaneous determination of periplocin and its two metabolites, periplocymarin and periplogenin in rat plasma: Application to a pharmacokinetic study

“…In addition, it has been reported that periplocin exhibited the effect on tumor cell apoptosis and the repression of tumor growth of hepatocellular carcinoma in vivo [3] and it could also inhibit cell growth and expression in colon cancer [4]. Meanwhile, periplocin demonstrated the ability of inhibiting the growth of lung cancer by down-regulating proteins [5] or by blocking the signaling pathways [6].…”

Early candidate biomarkers in urine of Walker-256 lung metastasis rat model

“…In addition, the expression level of aminoacylase-1A in human MCF-7 breast cancer cells was altered by 17β-estradiol (E2) treatment and so a might be potent target for treating breast cancer patients [65]. (6) The expression level of cluster of heat shock cognate 71 kDa protein was changed significantly when lung cancer cells were treated with periplocin, which revealed molecular mechanisms underlying the anti-cancer effects of periplocin on lung cancer cells [62]. In MCF-7 and MDA-MB-231 breast cancer cell lines, heat shock cognate 71 kDa protein was reported to be identified as specific phthalic acid-binding proteins [63].…”