Title:Mitochondria: A Promising Target for Anticancer Alkaloids
Volume: 13
Issue: 17
Author(s): Félix A. Urra, Miguel Cordova-Delgado, Hernan Pessoa-Mahana, Oney Ramírez-Rodríguez, Boris Weiss-Lopez, Jorge Ferreira and Ramiro Araya-Maturana
Affiliation:
Keywords:
Alkaloids, apoptosis, cancer cells, delivery, endoplasmic reticulum, mitochondria, targeting.
Abstract: A great number of alkaloids exhibit high potential in cancer research. Some of them are anticancer drugs with
well-defined clinical uses, exerting their action on microtubules dynamics or DNA replication and topology. On the other
hand, mitochondria have been recognized as an essential organelle in the establishment of tumor characteristics, especially
the resistance to cell death, high proliferative capacity and adaptation to unfavorable cellular environment. Interestingly,
many alkaloids exert their anticancer activities affecting selectively some functions of the tumor mitochondria by 1)
modulating OXPHOS and ADP/ATP transport, 2) increasing ROS levels and mitochondrial potential dissipation by crosstalk
between endoplasmic reticulum (ER) and mitochondria, 3) inducing mitochondria-dependent apoptosis and autophagy,
4) inhibiting mitochondrial metabolic pathways and 5) by alteration of the morphology and biogenesis of this organelle.
These antecedents show the relevance of developing research about the effects of alkaloids on functions controlled
by tumor mitochondria, offering an attractive target for the design of new alkaloid derivatives, considering organelle-
specific delivery strategies. This review describes mitochondria as a central component in the anticancer action of a
set of alkaloids, in a way to illustrate the importance of this organelle in medicinal chemistry.
