Abstract 4649: Apigenin increases maspin expression and suppresses invasiveness in prostate cancer cells
Authors: Shukla Sanjeev , Abbas Ata , Gupta Sanjay 
Published: August 2015

Acquisition of metastatic capability during prostate cancer progression leads to clinically incurable malignancy and accounts for the majority of deaths from this disease. Metastasis involves multiple processes, including invasion, intravasation, extravasation and tumor growth at the secondary site. Maspin, a unique member of the serpin (serine protease inhibitor) family, shown to regulate cell motility, invasion and contributes in tumor metastasis. Loss of maspin has been frequently identified in clinical prostate cancer specimens and prostate cancer cell lines, therefore novel therapeutic approaches to restore its expression are needed. Apigenin (4′, 5, 7-trihydroxyflavone), a plant flavone has shown to possess anticancer properties and alters pathways that regulate tumor cell invasion and metastasis, however molecular basis of these effects remains unclear. We demonstrate that apigenin enhances maspin expression in human prostate cancer cells through upregulation of p53 activity and downregulation of histone deacetylase (HDAC) activity. Treatment of human prostate cancer LNCaP cells (harboring wild type p53) with 1-40 μM apigenin for 72 h resulted in dose- and time- dependent decrease in cell invasion and migration with concurrent increase in maspin expression and increased its nuclear localization. Apigenin treatment also resulted in the inhibition of HDAC enzyme activity, increase in H3 and H4 acetylation and p53 activation, similar with the use of Class I HDAC inhibitor, trichostatin A. In human prostate cancer DU145 cells, harboring mutant p53, apigenin treatment resulted in an increase in maspin expression which correlated with upregulation of wild-type p53 activity, conversely trichostatin A was unable to upregulate maspin expression. Transfection of DU145 cells with maspin reporter plasmid increased the activity of maspin promoter, consistent with the results. In another approach, endogenous levels of mapsin was restored after transfection of cells with wild type p53 in prostate cancer PC-3 cells (p53 null), which was further increased by apigenin treatment. Furthermore, knockdown of HDAC1 did not affect maspin levels in human prostate cancer LNCaP and DU145 cell lines suggesting that HDAC1 inhibition does not play a role in maspin regulation, whereas it appears that apigenin-dependent global modulation of HDAC activity resulted in decreased cell invasion and proliferation. Taken together, our findings suggest that apigenin-mediated increase in maspin expression is regulated, in part, by p53 and its activation resulting in decreased invasiveness and migration capabilities of prostate cancer cells.

Citation Format: Sanjeev Shukla, Ata Abbas, Sanjay Gupta. Apigenin increases maspin expression and suppresses invasiveness in prostate cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4649. doi:10.1158/1538-7445.AM2015-4649