Ursolic Acid Impairs Cellular Lipid Homeostasis and Lysosomal Membrane Integrity in Breast Carcinoma Cells
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
Ursolic Acid Impairs Cellular Lipid Homeostasis and Lysosomal Membrane Integrity in Breast Carcinoma Cells. / Fogde, Ditte L.; Xavier, Cristina P.R.; Balnytė, Kristina; Holland, Lya K.K.; Stahl-Meyer, Kamilla; Dinant, Christoffel; Corcelle-Termeau, Elisabeth; Pereira-Wilson, Cristina; Maeda, Kenji; Jäättelä, Marja.
I: Cells, Bind 11, Nr. 24, 4079, 2022.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Ursolic Acid Impairs Cellular Lipid Homeostasis and Lysosomal Membrane Integrity in Breast Carcinoma Cells
AU - Fogde, Ditte L.
AU - Xavier, Cristina P.R.
AU - Balnytė, Kristina
AU - Holland, Lya K.K.
AU - Stahl-Meyer, Kamilla
AU - Dinant, Christoffel
AU - Corcelle-Termeau, Elisabeth
AU - Pereira-Wilson, Cristina
AU - Maeda, Kenji
AU - Jäättelä, Marja
N1 - Publisher Copyright: © 2022 by the authors.
PY - 2022
Y1 - 2022
N2 - Cancer is one of the leading causes of death worldwide, thus the search for new cancer therapies is of utmost importance. Ursolic acid is a naturally occurring pentacyclic triterpene with a wide range of pharmacological activities including anti-inflammatory and anti-neoplastic effects. The latter has been assigned to its ability to promote apoptosis and inhibit cancer cell proliferation by poorly defined mechanisms. In this report, we identify lysosomes as the essential targets of the anti-cancer activity of ursolic acid. The treatment of MCF7 breast cancer cells with ursolic acid elevates lysosomal pH, alters the cellular lipid profile, and causes lysosomal membrane permeabilization and leakage of lysosomal enzymes into the cytosol. Lysosomal membrane permeabilization precedes the essential hallmarks of apoptosis placing it as an initial event in the cascade of effects induced by ursolic acid. The disruption of the lysosomal function impairs the autophagic pathway and likely partakes in the mechanism by which ursolic acid kills cancer cells. Furthermore, we find that combining treatment with ursolic acid and cationic amphiphilic drugs can significantly enhance the degree of lysosomal membrane permeabilization and cell death in breast cancer cells.
AB - Cancer is one of the leading causes of death worldwide, thus the search for new cancer therapies is of utmost importance. Ursolic acid is a naturally occurring pentacyclic triterpene with a wide range of pharmacological activities including anti-inflammatory and anti-neoplastic effects. The latter has been assigned to its ability to promote apoptosis and inhibit cancer cell proliferation by poorly defined mechanisms. In this report, we identify lysosomes as the essential targets of the anti-cancer activity of ursolic acid. The treatment of MCF7 breast cancer cells with ursolic acid elevates lysosomal pH, alters the cellular lipid profile, and causes lysosomal membrane permeabilization and leakage of lysosomal enzymes into the cytosol. Lysosomal membrane permeabilization precedes the essential hallmarks of apoptosis placing it as an initial event in the cascade of effects induced by ursolic acid. The disruption of the lysosomal function impairs the autophagic pathway and likely partakes in the mechanism by which ursolic acid kills cancer cells. Furthermore, we find that combining treatment with ursolic acid and cationic amphiphilic drugs can significantly enhance the degree of lysosomal membrane permeabilization and cell death in breast cancer cells.
KW - autophagy
KW - cancer
KW - cationic amphiphilic drugs
KW - cell death
KW - lysosomal membrane permeabilization
KW - ursolic acid
U2 - 10.3390/cells11244079
DO - 10.3390/cells11244079
M3 - Journal article
C2 - 36552844
AN - SCOPUS:85144902263
VL - 11
JO - Cells
JF - Cells
SN - 2073-4409
IS - 24
M1 - 4079
ER -
ID: 330894366