Abstract 1410: Metabolic modulation of anaplastic thyroid cancer by Berberine: A targeted intervention

Abstract

Abstract Anaplastic thyroid cancer (ATC) is an undifferentiated thyroid cancer. A hallmark of ATC is increased inflammatory cytokine expression and inflammatory cell infiltration in the tumor microenvironment that is responsible for its aggressive nature. In contrast, papillary thyroid cancer (PTC) is well-differentiated and subsequently significantly less aggressive and more responsive to available therapies. The metabolic differences between ATC and PTC that correlate with differentiation status, and hence metastatic propensity, are poorly understood. Owing to its lack of differentiation, ATC is radioiodine therapy resistant, whereas differentiated thyroid cancers are susceptible. AMPK in the thyroid gland is responsible for glucose and iodine uptake. The AMPK pathway is a potential target for modulation due to the higher glucose uptake and metabolism associated with treatment resistance seen in ATC. Berberine, a naturally occurring plant alkaloid, regulates glycometabolism and lipid metabolism, improves energy expenditure, and reduces body weight. Exploration of a possible connection between the metabolic regulation displayed by BBR and AMPKα expression was warranted. Increased AMPKα signaling, observed through increased AMPKα phosphorylation, has an anti-tumor effect. When comparing PTC (TPC1) and ATC (T238) cell lines there was a 4.75- and 2.34-fold change, respectively, in phosphorylation of AMPKα upon BBR treatment. This demonstrates that BBR increases metabolic regulation in thyroid cancer cell lines, importantly, even when poorly differentiated. Further analysis of the correlation between differentiation status and metabolic characteristics between ATC and PTC was investigated using RNASeq. Differential gene expression was conducted to compare ATC and PTC using human thyroid cancer cell lines T238 and K1, respectively. These thyroid cancer cell lines were treated with 100 μM BBR or the same concentration of DMSO as a vehicle control for 24 hours. RNA was isolated from T238 and K1 cells and RNASeq was conducted by GeneWiz. This differential gene expression will help identify specific genes that are regulating metabolic patterns and is currently ongoing. Berberine (BBR) is a natural compound used widely in Traditional Chinese Medicine for its many pharmacological properties including anti-inflammatory, metabolic, antioxidant, and anti-cancer. BBR may be able to mitigate the metabolic pattern of ATC to potentially affect differentiation status as an intervening product. Intervention of the differentiation status of ATC will impact its progression, specifically metastasis. Therefore, identifying gene patterns that correlate with differentiation status will identify novel intervention targets for BBR. Citation Format: Kaci Kopec, Tara Jarboe, Mordechai Sternman, Nicole R. DeSouza, Sarnath Singh, Augustine Moscatello, Jan Geliebter, Raj K. Tiwari, Xiu-Min Li. Metabolic modulation of anaplastic thyroid cancer by Berberine: A targeted intervention [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1410.