Ursolic and oleanolic acids induce mitophagy in a549 human lung cancer cells

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

    Research output: Contribution to journalArticlepeer-review

    9 Scopus citations

    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 (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.

    Original languageEnglish
    Article number3444
    JournalMolecules
    Volume24
    Issue number19
    DOIs
    StatePublished - 23 Sep 2019

    Keywords

    • A549 human lung cancer cells
    • Mitophagy
    • oleanolic acid
    • PINK1/Parkin
    • Reactive oxygen species
    • Ursolic acid

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