Abstract 1775: Oncogenic reduction after exposure to capsaicin in oral squamous cell carcinoma

Abstract Background: Oral Squamous Cell Carcinoma (OSCC) is the sixth most common type of cancer worldwide with an increasing death rate of 0.6% each year from 2009 through 2021. Although there have been advances in the treatment, survival rates for oral cancer patients remain low, highlighting the need for alternatives. Capsaicin, an alkaloid compound that acts as a metabolite, could be a potential alternative for cancer treatment due to its anti-proliferative and apoptotic effect on cancer cells. Additionally, previous data from our lab has demonstrated an increased cell viability in OECM-1 cells when treated with Lipopolysaccharides (LPS) from P. gingivalis. Therefore, in this study, we evaluated the effects of capsaicin on the viability, proliferation, and migration of the OSCC cell line OECM-1 with and without P. gingivalis LPS treatment. Methodology: Cell viability was measured by AlamarBlue after 24 and 48 hours (h) of treatment with capsaicin using serial dilutions starting at 1000μM and calculated capsaicin's half-maximal inhibitory concentration (IC50). Cell proliferation was measured by seeding 150, 000 cells per well and counting with TrypanBlue the change in cell number after treatment with capsaicin (100μM and 200μM) for 24h and 48h. Cell migration was assessed by wound healing assays, in which the length of the wound was measured before and after exposure to treatment by calculating the percentage of wound closure after 24h and 48h. We also measured the impact of capsaicin in the proliferation and migration of OSCC cells using a combination of capsaicin (100μM and 200μM) and LPS derived from P. gingivalis (4ng/mL and 8ng/mL). Results: Higher concentrations of capsaicin reduced cell viability at both timepoints with IC50s of 470uM and 398uM at 24h and 48h, respectively. While cell proliferation increased at 24h of exposure to capsaicin at only 200μM (p=0.010), cell proliferation significantly decreased at both 100μM and 200μM of capsaicin after 48h (p=0.004 and p=0.005, respectively). Higher concentrations of capsaicin decreased the percentage of closure of the wound at both timepoints. On the other hand, cell proliferation decreased when treated with P. gingivalis LPS (4ng/mL) and 100μM (p=0.016) and 200μM (p=0.029) of capsaicin at 48h. In the wound healing assay, both concentrations of capsaicin with P. gingivalis LPS (8ng/mL) presented a decreased percentage of closure of the wound. Conclusion: Capsaicin was able to reduce oncogenic phenotypes in OSCC and counteract the proliferative effects of P. gingivalis LPS. Understanding the molecular impact of capsaicin in OSCC may lead to a novel treatment strategy. Citation Format: Samira B. Abdullah-Vargas, Riseilly Ramos-Nieves, Angel J. Amaral-Maisonet, Amanda Prats-Marrero, Jeannette L. Salgado-Montilla, Gabriel Borges-Vélez, Josué Pérez-Santiago. Oncogenic reduction after exposure to capsaicin in oral squamous cell carcinoma [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 1775.