Anti-cancer Activity of Allium jesdianum Extract Loaded on Microemulsions on Colon Cancer Cells Through Suppression of Autophagy and Activation of Necroptosis Process

Abstract

Background: Natural products such as Allium jesdianum (AJ) have pharmacological properties with negligible side effects. However, their therapeutic potential has been limited by their low bioavailability. Nanocarriers improve the bioavailability and stability of flavonoids as the most common polyphenolic antioxidant. Objectives: This study aimed to assess the toxic effects of Allium jesdianum extract (AJE) loaded in microemulsion (AJE-ME) on the HT-29 cells, a human colon cancer cell line. Methods: HT-29 cells were exposed to 50 µM/mL of AJE or AJE-ME for 24 h. Colony formation, cell viability percentage, flow cytometry, and gene expression studies were carried out to assess the impacts of the AJE-ME. Results: The AJE-ME with the required characteristics and a slow-release AJE were prepared. AJE-ME significantly diminished the survival percentage and colony formation of HT-29 cells compared to the free AJE. Upregulation of mTOR and downregulation of Beclin1 and Atg5 indicated suppression of autophagy by the AJE-ME. Flow cytometry results showed that AJE-ME significantly increased the percentage of necrosis in the HT-29 cells. AJE-ME upregulated the expression of necroptosis-related genes such as receptor-interacting protein kinase 3 (RIP3) and mixed lineage kinase domain-like pseudokinase (MLKL). Conclusions: These data collectively demonstrated that ME enhanced the toxic effect of AJE against human colon cancer cells by suppressing autophagy and activating necroptosis.