Abstract
Triple negative breast cancer(TNBC) has generated growing interests due to its aggressive biologic behavior and absence of targeted therapy approach. Glycyrrhizin(GL) from licorice root and its metabolite, glycyrrhetinic acid(GA) have shown extensive bioactivities in clinic. Here, we demonstrate that GL and GA have contrary anti-cancer effect on TNBC MDA-MB-231 cells. Beside its inhibition of cell proliferation, GA at non-cytotoxic concentration showed synergistic effect in combination with anti-cancer drug, etoposide(VP-16). Specifically, GA enhanced cytotoxicity through regulating topoisomerase IIα(TOPO 2A) targeted by etoposide. GA sensitized the cells to etoposide through elevating TOPO 2A with a 2.4 fold rate at 12h. From 12 to 48h, GA halved the expression of TOPO 2A and stimulated apoptosis, which exhibited its antineoplastic effect. Our experiments showed that GSH depletion, modulation of MAPK and AKT pathways accounted for the regulation of topoisomerase IIα and apoptosis. However, GL showed protection and detoxication by decreasing reactive oxygen species generation, maintaining GSH and differentially modulating apoptosis, AKT pathway, ERK and JNK of MAPK pathway. Collectively, our results demonstrate that GA, instead...Continue Reading
Citations
Jan 17, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ichiaki ItoFujio Suzuki
Jul 2, 2020·Natural Product Research·Bharat GoelShreyans K Jain
Jan 29, 2019·Journal of Biomolecular Structure & Dynamics·Aparna ShuklaFeroz Khan
Feb 23, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Daniela P S AlhoSilvia Marin
Aug 17, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Daniela P S AlhoSilvia Marin
Nov 22, 2018·Frontiers in Immunology·Xiaogang XuWeifen Li
May 20, 2020·Cancer Management and Research·Hao WangJiazeng Xia
Jan 1, 2021·Bioorganic & Medicinal Chemistry·Pinar AlperFerda Ari
Nov 20, 2019·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Ali DehshahriGautam Sethi
Jan 9, 2021·Evidence-based Complementary and Alternative Medicine : ECAM·Bo WangYue Zhang
Mar 16, 2021·Critical Reviews in Oncology/hematology·RamaRao MallaGanji Purnachandra Nagaraju
Sep 17, 2020·European Journal of Medicinal Chemistry·Rajibul Islam, Kok Wai Lam
Oct 16, 2019·Current Medicinal Chemistry·Kun ChenHai-Liang Zhu
Jul 3, 2021·International Journal of Molecular Sciences·Ying SunHao Hu
Jul 17, 2021·Free Radical Biology & Medicine·Yi WenJianping Chen
Jul 27, 2021·International Journal of Pharmaceutics·Niloufar Hosseini-GivMaryam M Matin
Aug 13, 2021·Frontiers in Pharmacology·Yunhui FengRunyue Huang
Dec 9, 2021·Nutrition and Cancer·Jiayuan PengYanfeng Zhu