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Article Publish Status: FREE
Abstract Title:

Ursolic and Oleanolic Acids Induce Mitophagy in A549 Human Lung Cancer Cells.

Abstract Source:

Molecules. 2019 Sep 23 ;24(19). Epub 2019 Sep 23. PMID: 31547522

Abstract Author(s):

Nayeli Shantal Castrejón-Jiménez, Kahiry Leyva-Paredes, Shantal Lizbeth Baltierra-Uribe, Juan Castillo-Cruz, Marcia Campillo-Navarro, Alma Delia Hernández-Pérez, Alexandra Berenice Luna-Angulo, Rommel Chacón-Salinas, Ramón Mauricio Coral-Vázquez, Iris Estrada-García, Luvia Enid Sánchez-Torres, Carlos Torres-Torres, Blanca Estela García-Pérez

Article Affiliation:

Nayeli Shantal Castrejón-Jiménez

Abstract:

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 (Δψ) 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.

Study Type : In Vitro Study

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