Targeting Mitochondrial Therapy in the Regulation of HPV Infection and HPV-Related Cancers.

Abstract

It has been previously proposed that some types of cancer cells reprogram their metabolic pathways, favoring the metabolism of glucose by aerobic glycolysis (Warburg effect) instead of oxidative phosphorylation, mainly because the mitochondria of these cells are damaged, thus displaying mitochondrial dysfunction. However, in several cancers, the mitochondria do not exhibit any dysfunction and are also necessary for the tumor's growth and maintenance. Remarkably, if the mitochondria are dysfunctional, specific processes associated with the release of cytochrome c (cyt c), such as apoptosis, are significantly impaired. In these cases, cellular biotherapies such as mitochondrial transplantation could restore the intrinsic apoptotic processes necessary for the elimination of cancers. On the other hand, if the mitochondria are in good shape, drugs that target the mitochondria are a valid option for treating the related cancers. Famously, the mitochondria are targeted by the human papillomavirus (HPV), and HPV-related cancers depend on the host's mitochondria for their development and progression. On the other hand, the mitochondria are also important during treatment, such as chemotherapy, since they are key organelles for the increase in reactive oxygen species (ROS), which significantly increases cell death due to the presence of oxidative stress (OS). In this way, the mitochondria in HPV infection and in the development of HPV-related cancer could be targeted to reduce or eliminate HPV infections or HPV-related cancers. To our knowledge, there was no previous review specifically focusing on this topic, so this work aimed to summarize for the first time the potential use of mitochondria-targeting drugs, providing molecular insights on the main therapeutics developed so far in HPV infection and HPV-related cancer. Thus, we reviewed the mechanisms associated with HPV-related cancers, with their early proteins and mitochondrial apoptosis specifically induced by different compounds or drugs, in which these molecules induce the production of ROS, the activation of proapoptotic proteins, the deactivation of antiapoptotic proteins, the loss of mitochondrial membrane potential (Δψm), cyt c release, and the activation of caspases, which are all events which lead to the activation of mitochondrial apoptosis pathways. This makes these compounds and drugs potential anticancer therapeutics that target the mitochondria and could be exploited in future biomedical strategies.