Abstract C169: ER maleate is a novel anticancer agent in oral cancer cells: Implications for cancer therapy

Abstract

Abstract ER maleate was investigated as a novel anticancer agent for oral squamous cell carcinoma (OSCC), the most common head and neck squamous cell carcinoma (HNSCC). We identified its putative molecular targets, demonstrated their clinical relevance, and showed its chemosensitization potential for platinum drugs to aid in HNSCC management. Biologic effects of ER maleate were determined on cell proliferation, spheroid/colony formation, caspase activity, cell migration and invasion in vitro and using oral tumor xenografts in vivo. mRNA profiling, real time PCR and western blot suggested ER maleate modulated the expression of polo-like kinase 1 (PLK1) and spleen tyrosine kinase (Syk). Their clinical significance was determined in oral SCC patients by immunohistochemistry and correlated with prognosis by Kaplan-Meier survival analysis. ER maleate induced cell apoptosis, inhibited proliferation, colony formation, migration and invasion in oral cancer cells. Imagestream analysis revealed cell cycle arrest in G2/M phase and increased polyploidy, unravelling deregulation of cell division and cell death. Mechanistically, ER maleate decreased expression of PLK1 and Syk, induced cleavage of PARP, caspase 9 and caspase 3 and increased chemosensitivity to carboplatin; significantly suppressed tumor growth and increased antitumor activity of carboplatin in tumor xenografts. ER maleate treated tumor xenografts showed reduced PLK1 and Syk expression; clinical investigations revealed overexpression of PLK1 and Syk in oral SCC patients that correlated with disease prognosis. In conclusion, our in vitro and in vivo findings provide a strong rationale for pre-clinical efficacy of ER maleate as a novel anti-cancer agent and chemosensitizer of platinum drugs for OSCC. Citation Format: Guodong Fu, Sr.. ER maleate is a novel anticancer agent in oral cancer cells: Implications for cancer therapy. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr C169.