Abstract 5794: Targeting CD133+/CD90+ liver cancer stem cells by piperlongumine: A novel strategy for liver cancer treatment

Abstract

Abstract Liver cancer is an aggressive malignant disease. It’s the most common cancer worldwide and the leading cause of cancer death. Because of the atypical early symptoms of liver cancer, the majority of liver cancer patients are diagnosed with advanced-cancer stage, decreasing the chance of resection and resulting in a poor survival rate. Liver cancer stem cells (LCSCs) are a small subpopulation inside the tumor bulk, characterized by the maintenance of self-renewal and pluripotency. Thus, LCSCs are responsible for cancer initiation, metastasis, relapse, and chemoresistance. Elucidating LCSC characteristics and disclosing their regulatory mechanism might facilitate the development of prognostic, diagnostic, and therapeutic approaches to improve the clinical management of liver cancer. Piperlongumine (PL) an active biological pyridine alkaloid has anti-angiogenic, anti-diabetic, and anti-bacterial activities. The present study aimed to isolate highly tumorigenic and aggressive subpopulation of LCSCs (CD133+/CD90+) from primary tumors and different cell lines and investigate the effect of (PL), a novel targeting therapy, on LCSCs proliferation. The isolated LCSCs were treated with different concentrations of PL and its effect was examined by cell viability, cell morphological changes, western blot, caspase-3 activity, apoptotic induction, and clonogenic formation. By using Immunocytochemistry (ICC) analysis, the localization of nuclear and cytoplasmic Aldehyde dehydrogenase (ALDH6A1) was detected. PL inhibited the viability of CD133+/CD90+LCSC-sub-popupation and caused morphological changes after 48 hours while enhancing the pre-apoptotic signals and caspase-3 activity. In addition, PL decreased the colonies’ formation ability compared to control group. Furthermore, PL suppressed the protein expression levels of ALDH6A1, Notch-1, β-catenin, ERK1/2, and Cyclin-D1 in the dose and time-dependent manners. Besides, PL decreased the localization and intensity of nuclear and cytoplasmic ALDH6A1 compared to the control group, indicating that PL decreased the proliferation and stemness markers of LCSCs. Overall, Piperlongumine as a novel targeting therapy has an important role in targeting CD133+/CD90+ LCSCs sub-population proliferation. Citation Format: Basma A. Abdelaziz, Omayma M. Sadek, Ahmed S. Sultan. Targeting CD133+/CD90+ liver cancer stem cells by piperlongumine: A novel strategy for liver cancer treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5794.