Abstract 6932: Phloroglucinol suppresses metastasis in CAV1 overexpressing cancer cells

Abstract Metastasis is the process by which malignant cells dissociate from a primary tumor and disseminate to distant organs or tissues. This phenomenon presents one of the most significant challenges in oncology, as it is strongly associated with poor clinical outcomes and increased mortality rates. Caveolin-1 (CAV1) plays a crucial role in the metabolic reprogramming of cancer cells, particularly by promoting glycolysis, which enhances tumor cell migration and metastasis. This study aimed to evaluate the anti-metastatic potential of phloroglucinol, a monomer of phlorotannins from brown algae with anti-tumorigenic effects. The effects of phloroglucinol were assessed in metastatic breast (MDA-MB-231) and melanoma (B16-F10) cells expressing or not CAV1. Cell viability, migration, hexokinase activity and L-lactate levels were analyzed. C57BL/6 mice (N=5) were injected with B16-F10 cells pre-treated with phloroglucinol, and after 21 days, lung metastasis was assessed. In vitro, phloroglucinol significantly inhibited the migration of CAV1-expressing cancer cells and reduced lactate levels in the supernatants of the treated cells. Additionally, phloroglucinol suppressed CAV1-enhanced glycolysis by inhibiting hexokinase activity. In vivo, pre-treatment with phloroglucinol reduced the metastatic potential of CAV1-overexpressing cells. These findings suggest that phloroglucinol holds promise as a novel therapeutic agent for preventing cancer metastasis by targeting cancer cell metabolism. Funding: ANID FONDECYT Iniciación [11230112] (L.S.), ANID-FONDECYT-Regular [1210644] (A.F.G.Q.), Fondo de Investigación Avanzada en Áreas Prioritarias (FONDAP) Grant 15130011 and 1523A0008 (A.F.G.Q.). Citation Format: Layla Simon, Keila Torres, Andrew F. Quest. Phloroglucinol suppresses metastasis in CAV1 overexpressing cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6932.