TY - JOUR
T1 - Ursolic and oleanolic acids induce mitophagy in a549 human lung cancer cells
AU - Castrejón-Jiménez, Nayeli Shantal
AU - Leyva-Paredes, Kahiry
AU - Baltierra-Uribe, Shantal Lizbeth
AU - Castillo-Cruz, Juan
AU - Campillo-Navarro, Marcia
AU - Hernández-Pérez, Alma Delia
AU - Luna-Angulo, Alexandra Berenice
AU - Chacón-Salinas, Rommel
AU - Coral-Vázquez, Ramón Mauricio
AU - Estrada-García, Iris
AU - Sánchez-Torres, Luvia Enid
AU - Torres-Torres, Carlos
AU - García-Pérez, Blanca Estela
N1 - Publisher Copyright:
© 2019 by the authors.
PY - 2019/9/23
Y1 - 2019/9/23
N2 - Ursolic and oleanolic acids are natural isomeric triterpenes known for their anticancer activity. Here, we investigated the effect of triterpenes on the viability of A549 human lung cancer cells and the role of autophagy in their activity. The induction of autophagy, the mitochondrial changes and signaling pathway stimulated by triterpenes were systematically explored by confocal microscopy and western blotting. Ursolic and oleanolic acids induce autophagy in A549 cells. Ursolic acid activates AKT/mTOR pathways and oleanolic acid triggers a pathway independent on AKT. Both acids promote many mitochondrial changes, suggesting that mitochondria are targets of autophagy in a process known as mitophagy. The PINK1/Parkin axis is a pathway usually associated with mitophagy, however, the mitophagy induced by ursolic or oleanolic acid is just dependent on PINK1. Moreover, both acids induce an ROS production. The blockage of autophagy with wortmannin is responsible for a decrease of mitochondrial membrane potential (D) and cell death. The wortmannin treatment causes an over-increase of p62 and Nrf2 proteins promote a detoxifying effect to rescue cells from the death conducted by ROS. In conclusion, the mitophagy and p62 protein play an important function as a survival mechanism in A549 cells and could be target to therapeutic control.
AB - Ursolic and oleanolic acids are natural isomeric triterpenes known for their anticancer activity. Here, we investigated the effect of triterpenes on the viability of A549 human lung cancer cells and the role of autophagy in their activity. The induction of autophagy, the mitochondrial changes and signaling pathway stimulated by triterpenes were systematically explored by confocal microscopy and western blotting. Ursolic and oleanolic acids induce autophagy in A549 cells. Ursolic acid activates AKT/mTOR pathways and oleanolic acid triggers a pathway independent on AKT. Both acids promote many mitochondrial changes, suggesting that mitochondria are targets of autophagy in a process known as mitophagy. The PINK1/Parkin axis is a pathway usually associated with mitophagy, however, the mitophagy induced by ursolic or oleanolic acid is just dependent on PINK1. Moreover, both acids induce an ROS production. The blockage of autophagy with wortmannin is responsible for a decrease of mitochondrial membrane potential (D) and cell death. The wortmannin treatment causes an over-increase of p62 and Nrf2 proteins promote a detoxifying effect to rescue cells from the death conducted by ROS. In conclusion, the mitophagy and p62 protein play an important function as a survival mechanism in A549 cells and could be target to therapeutic control.
KW - A549 human lung cancer cells
KW - Mitophagy
KW - PINK1/Parkin
KW - Reactive oxygen species
KW - Ursolic acid
KW - oleanolic acid
UR - http://www.scopus.com/inward/record.url?scp=85072572277&partnerID=8YFLogxK
U2 - 10.3390/molecules24193444
DO - 10.3390/molecules24193444
M3 - Artículo
C2 - 31547522
AN - SCOPUS:85072572277
SN - 1420-3049
VL - 24
JO - Molecules
JF - Molecules
IS - 19
M1 - 3444
ER -