Abstract 4274: Anticancer mechanisms of a small amphipathic molecule, LTX-401, against B16 melanoma cancer cells

Abstract

Abstract In the present study we investigated the mechanism behind the killing of B16F1 murine melanoma cells by the small amphipathic β(2,2)-amino acid derivative, LTX-401 (Mw<500Da). In vitro, LTX-401 induced lytic cell death and the release of Danger-Associated-Molecular-Pattern Molecules(DAMPs) such as ATP and HMGB-1. In addition, the cells released pro-Cathepsin-B and cytochrome-c following LTX-401 treatment. Flow cytometry and confocal microscopy studies revealed reduced signal from the lysomal dye Lysotracker-DND-26, indicating loss of lysomal integrity. Furthermore, flow cytometry analysis showed that the mitochondrial membrane potential was unaffected in the LTX-401 treated cells. Transmission electron microscopy of LTX-401 treated cells showed little or no ultra structural changes in the mitochondria. The in vivo antitumor effect of LTX-401 against intradermally established B16F1 melanoma was assessed in syngeneic mice. Intratumoral administration of the molecule caused rapid tumor necrosis and complete tumor regression in the majority of the animals treated. In conclusion, these findings demonstrate that LTX-401 has the ability to cause immunogenic cell death in cancer cells and induce complete tumor regression in solid tumors and thus might have a potential as an immunotherapeutic agent. Citation Format: Liv-Marie Eike, Brynjar Mauseth, Ketil Camilio, Oystein Rekdal, Baldur Sveinbjornsson. Anticancer mechanisms of a small amphipathic molecule, LTX-401, against B16 melanoma 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 4274. doi:10.1158/1538-7445.AM2015-4274