Abstract 5565: Antitumor activities of psammaplin A analogues in human lung cancer cells

Abstract

Abstract Histone deacetylase inhibitors (HDACi) are considered to be potential candicates for cancer therapeutic agents. HDACi suppresses the progression of tumorigenesis through epigenetic regulation of target protein acetylation. Psammaplin A (PsA), originated from a marine product Pseudoceratina purpurea, also showed a potential HDAC inhibition. Based on the potential anticancer activity of PsA, various PsA analogs were designed and synthesized to explore novel candidates in the development of anticancer agents. Among compounds tested, a β-napthyl-derivertive of PsA (compound 30) exhibited a strong growth-inhibitory activity against human lung cancer cells and the activity was comparable to PsA. Compound 30 also effectively inhibited HDAC and up-regulated the level of ac-Histone3, p-AKT, p-ERK in human A549 lung cancer cells. In in vivo xenograft animal model implanted A549 cells, the administration of compound 30 intraperitoneally for 35 days exhibited a potential growth inhibitory activity of the tumor (47.6% inhibition at 30 mg/kg). The immunohistochemical analysis of tumor tissues also revealed the inhibition of the cell proliferation biomarker Ki-67 expression by compound 30. Taken together, these data suggest that a β-napthyl analog of PsA has the potential antitumor activity and thus to be prioritized in the development of cancer chemotherapeutic agents. Citation Format: Yoonho Shin, Suckchang Hong, Jongheon Shin, Hyeung-geun Park, Sang Kook Lee. Antitumor activities of psammaplin A analogues in human lung 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 5565. doi:10.1158/1538-7445.AM2015-5565