RRC ID 62745
Author Yoshinaga A, Kajiya N, Oishi K, Kamada Y, Ikeda A, Chigwechokha PK, Kibe T, Kishida M, Kishida S, Komatsu M, Shiozaki K.
Title NEU3 inhibitory effect of naringin suppresses cancer cell growth by attenuation of EGFR signaling through GM3 ganglioside accumulation.
Journal Eur J Pharmacol
Abstract Naringin, which is one of the flavonoids contained in citrus fruits, is well known to possess various healthy functions to humans. It has been reported that naringin suppresses cancer cell growth in vitro and in vivo, although the underlying mechanisms are not fully understood. Recently, the roles of glycoconjugates, such as gangliosides, in cancer cells have been focused because of their regulatory effects of malignant phenotypes. Here, to clarify the roles of naringin in the negative-regulation of cancer cell growth, the alteration of glycoconjugates induced by naringin exposure and its significance on cell signaling were investigated. Human cancer cells, HeLa and A549, were exposed to various concentrations of naringin. Naringin treatment induced the suppression of cell growth toward HeLa and A549 cells accompanied with an increase of apoptotic cells. In naringin-exposed cells, GM3 ganglioside was drastically increased compared to the GM3 content prior to the treatment. Furthermore, naringin inhibited NEU3 sialidase, a GM3 degrading glycosidase. Similarly, NEU3 inhibition activities were also detected by other flavanone, such as hesperidin and neohesperidin dihydrocalcone, but their aglycones showed less inhibitions. Naringin-treated cancer cells showed suppressed EGFR and ERK phosphorylation levels. These results suggest a novel mechanism of naringin in the suppression of cancer cell growth through the alteration of glycolipids. NEU3 inhibitory effect of naringin induced GM3 accumulation in HeLa and A549 cells, leading the attenuation of EGFR/ERK signaling accompanied with a decrease in cell growth.
Volume 782
Pages 21-9
Published 2016-7-5
DOI 10.1016/j.ejphar.2016.04.035
PII S0014-2999(16)30249-7
PMID 27105818
MeSH Apoptosis / drug effects Cell Proliferation / drug effects ErbB Receptors / metabolism* Extracellular Signal-Regulated MAP Kinases / metabolism Flavanones / pharmacology* G(M3) Ganglioside / metabolism* Glycoconjugates / metabolism Glycoside Hydrolase Inhibitors / pharmacology* HeLa Cells Humans Neuraminidase / antagonists & inhibitors* Phosphorylation / drug effects Signal Transduction / drug effects* Up-Regulation / drug effects
IF 3.263
Human and Animal Cells HeLa A549