Molecular mechanisms of ischemic preconditioning and postconditioning as putative therapeutic targets to reduce tumor survival and malignancy.
In tumors intermittent hypoxia has been reported to be more representative than normoxia or continuous exposure to low oxygen concentrations. Intermittent hypoxia is thought to increase tumor resistance against both anti-cancer therapy and the sustained ischemia that randomly occurs because of the dynamic nature of tumor vasculature. Here, we hypothesize that the molecular mechanisms underlying intermittent hypoxia in tumor cells share some triggers, modulators, and end-effectors of the intermittent episodes of ischemia and reperfusion that characterize ischemic preconditioning and postconditioning. These are among the most effective maneuvers protecting cells from ischemia-reperfusion injury. If this hypothesis were confirmed, several well-investigated molecular mediators of pre/post-conditioning could be explored as therapeutic targets against tumor malignancy. For examples, drugs that completely block the cardioprotection induced by ischemic preconditioning, such as mitochondrial potassium ATP channel inhibitors or mitochondrial permeability transition pore openers, could be extraordinarily efficient in counteracting the adaptations of tumor cells and cancer stem cells to intermittent hypoxia. As a consequence, this strategy should be effective in blunting tumor capacity to progress toward malignancy and survive in ischemic conditions.
Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy; National Institute for Cardiovascular Research, Bologna, Italy; BioEngLab, Health Science and Technology-Interdepartmental Center for Industrial Research (HST-CIRI), University of Bologna, Ozzano Emilia (BO), Italy. Electronic address: claudio.muscari@unibo.it.
Claudio
C
Muscari
Emanuele
E
Giordano
Francesca
F
Bonafè
Marco
M
Govoni
Alice
A
Pasini
Carlo
C
Guarnieri
D000222:Adaptation, Physiological / Q000502:physiology*; D015687:Cell Hypoxia / Q000502:physiology*; D006801:Humans; D057775:Ischemic Postconditioning / Q000379:methods*; D019194:Ischemic Preconditioning / Q000379:methods*; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy / Q000503:physiopathology*