Abstract Title:

Anti-proliferative and cytotoxic activities of the flavonoid isoliquiritigenin in the human neuroblastoma cell line SH-SY5Y.

Abstract Source:

Chem Biol Interact. 2019 Feb 1 ;299:77-87. Epub 2018 Nov 28. PMID: 30502331

Abstract Author(s):

Stephane J de M Escobar, Genevieve M Fong, Sheila M B Winnischofer, Martin Simone, Lenka Munoz, Joanne M Dennis, Maria Eliane M Rocha, Paul K Witting

Article Affiliation:

Stephane J de M Escobar


Neuroblastoma is a common childhood cancer with high mortality. We evaluated the capacity of the flavonoid, isoliquiritigenin (4,2',4'-trihydroxychalcone; ISL) to inhibit cellular proliferation and migration in the human neuroblastoma cell line SH-SY5Y. Incubation of cultured SH-SY5Y cells with 20-100 μM ISL decreased cell confluency (15-70%) after 24 h incubation, while 10-100 μM ISL (24 h) depleted intracellular ATP stores (15-90% vs vehicle-treated control) after 24 h incubation. ISL-mediated cell toxicity did not involve intracellular caspase 3/7 activation, externalization of phosphatidylserine on the cell membrane or stimulation of TNF and IL-1β release, all indicating that the flavonoid did not induce apoptosis. Pre-treatment of cells with necrostatin-1, a necroptosis inhibitor, significantly restored ATP levels (ATP levels increased 12-42%) in ISL-treated neuroblastomacells indicative of enhanced viability. By contrast, RIP1 phosphorylation status remained unchanged in cells treated with ISL although the intracellular ratio of phosphorylated/total parental RIP1 increased after ISL treatment on SH-SY5Y cells indicating that ISL decreased levels of native RIP1. Inaddition, ISL treatment inhibited SH-SY5Y cell migration/proliferation in a scratch assay and arrested cell cycle transition by significantly decreasing the number of cells in G0/G1 phase and increasing populations by ~10% in S (primarily) and G2/M (lesser extent) phases. The intracellular ratio ofphosphorylated/total ERK 1/2 and p38 remained unchanged after ISL treatment (up to 40 μM); ERK activation was only determined at ISL dose well above the experimental ICvalue as judged by ELISA analyses and this did not correlate with ISL cytotoxicity at lower dose<40 μM; Western blot assay confirmed the detection of phosphorylated (p-)ERK1/2 and (p-)p38 in ISL treated cells. Together the results suggest that ISL exerts anti-proliferative and cytotoxic activity on SHSY5Y cells through the loss of ATP, induction of cell cycle arrest, and cell death largely viaa necroptotic mechanism in the absence of apoptotic activity.

Print Options

Sayer Ji
Founder of GreenMedInfo.com

Subscribe to our informative Newsletter & get Nature's Evidence-Based Pharmacy

Our newsletter serves 500,000 with essential news, research & healthy tips, daily.

Download Now

500+ pages of Natural Medicine Alternatives and Information.

This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.

© Copyright 2008-2020 GreenMedInfo.com, Journal Articles copyright of original owners, MeSH copyright NLM.