Abstract 2186: Galangin effectively inhibits the proliferation and stemness characteristics of liver cancer stem cells by knocking down the expression of TINCR.

Abstract Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. Liver cancer stem cells (LCSCs) are thought to play a crucial role in its pathology, but their mechanisms in HCC remain poorly understood. TINCR (terminal differentiation-induced long non-coding RNA) influences cancer cell behavior in various malignancies, including HCC. Recent research has highlighted the potential of natural anticancer agents, particularly Galangin (GLN). This compound is recognized for its antibacterial, antifungal, and antiviral properties, and it may also contribute to managing conditions like hypertension, diabetes, and cancer prevention. However, the specific effects of GLN on HCC are still not fully understood. The present study aims to explore the molecular mechanism and anticancer properties of GLN on TINCR expression, which may influence the stemness characteristics of liver cancer stem cells (LCSCs). Our findings demonstrate that TINCR is highly expressed in LCSCs, suggesting that it is essential for maintaining the stemness properties and tumorigenesis of these cells. In the Wst-1 assay, GLN treatment exhibited a dose-dependent inhibitory effect on proliferation and induced significant morphological changes in LCSCs, indicative of apoptosis induction after 24 h of treatment. Furthermore, the expression of TINCR was significantly inhibited after 24 h of GLN treatment compared to the control. Western blot analysis and qRT-PCR were conducted to assess oncogenic signaling pathways, including β-catenin, mTOR, and STAT3, along with downstream targets. Our results indicated a significant reduction in cell viability and oncogenic signals, as well as in LCSC stemness markers, following GLN treatment combined with TINCR knockdown, suggesting that inhibiting TINCR expression alongside GLN treatment effectively disrupts oncogenic signals and inhibits LCSC stemness characteristics. In addition, TINCR knockdown significantly enhanced the antiproliferative effects and sensitivity to Doxorubicin. Our data introduce GLN as a promising, natural, and non-toxic anticancer compound, demonstrating its therapeutic potential for treating HCC by regulating the expression pattern of TINCR. Citation Format: Amira S. Fyala, Mohamed M. H Elkewedi, Ahmed S. Sultan. Galangin effectively inhibits the proliferation and stemness characteristics of liver cancer stem cells by knocking down the expression of TINCR [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2186.