Allium jesdianum Extract Induces Oxidative Stress and Necroptosis in Human Colorectal Cancer (HT-29) Cell Line

Abstract

This study aimed to evaluate the toxic impact of hydro-alcoholic Allium jesdianum extract (AJE) on the growth of HT-29 human colorectal cancer cell line. Phytochemical analysis using gas chromatography and mass spectroscopy (GCMS) was done to determine the bioactive components of AJE. HT-29 cells exposed to 0 (control), 25, 50, and 100 g/mL of AJE for 48 hours. Cell survival, colony numbers, flow cytometry, oxidative stress, and gene expression were examined to evaluate the toxic impacts of the AJE. Twelve different phyto-constituents with peak areas were determined by the GCMS analysis. The major compounds were Allicin and α-Pinene. AJE considerably reduced the viability and colony numbers of the HT-29 cells. The AJE concentration-dependently increased necrosis, but not apoptosis in the HT-29 cells. AJE upregulated the expression of necroptosis-associated genes including RIPK1, RIPK3, and MLKL in a concentration-dependent manner. AJE also dose-dependently enhanced MDA contents and reactive oxygen species (ROS) level and diminished antioxidant enzyme level in the HT-29 cells. These data collectively indicated that AJE prevented the growth of the HT-29 cells by inducing oxidative stress, and activation necroptosis signaling pathways. HIGHLIGHTS Allium jesdianum extract inhibits proliferation of HT-29 cells  Allium jesdianum extract induces necroptosis in HT-29 cells  Allium jesdianum extract induces oxidative stress in HT-29 cells 2 Alidadi, H; et al.

Necroptosis: A Pathogenic Negotiator in Human Diseases

“…In-depth, noalbaconol triggered necroptosis through promoting downregulation of E3-ubiquitin ligases, proteasomal degradation of cIAP1/2 and TRAFs protein to prevent RIPK1 ubiquitination caused by RIPK3-mediated ROS generation. The increased levels of ROS are also a regulative factor in several other types of naturally derived necroptosis inducers such as 2-methoxy-6-acetyl-7-methyljuglone [ 249 , 250 , 251 ], 11-methoxytabersonine (11-MT) [ 252 ], Allium jesdianum [ 253 ], Arctigenin [ 254 ], Columbianadin [ 255 ], Matrine [ 256 ], Natural Polyphyllins D [ 257 ], Pristimerin [ 258 ] and Trichothecin [ 259 ], thus further confirming their anti-carcinogenic role via necroptosis induction. Berberine induces necroptosis in ovarian cancer cells and MYC-overexpressing lymphomas by promoting mitophagy-mediated RIPK1/3 activation and necrosome complex formation [ 260 , 261 ].…”

Protective effect of Allium jesdianum in an Alzheimer's disease induced rat model

“…Allium jesdianum Boiss & Bushe is a species of bulbous plant in the genus Allium and belongs to the Alliaceae family and is grown in the Zagros Mountains of Iran. According to research, A. jesdianum has some useful antioxidant, antipyretic, antibacterial, and antifungal properties (Alidadi et al 2021;Sohrabinezhad et al 2019).…”