Mitochondria: A Promising Target for Anticancer Alkaloids

Félix   A.   Urra; Miguel      Cordova-Delgado; Hernan      Pessoa-Mahana; Oney      Ramírez-Rodríguez; Boris      Weiss-Lopez; Jorge      Ferreira; Ramiro      Araya-Maturana

doi:10.2174/15680266113139990150

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.

Keywords: Alkaloids, apoptosis, cancer cells, delivery, endoplasmic reticulum, mitochondria, targeting.

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