Mitochondria as a target in cancer treatment

Abstract

Mitochondria are biosynthetic, bioenergetic, and signaling organelles existing in almost all eukaryotic cells, and their dysregulated function has been proved to be essential for tumorigenesis, tumor development, and tumor metastasis. In this short review, first, we briefly summarize the historic misunderstanding of mitochondria in tumors, and then come up with a current view that mitochondria play a pivotal role in tumor cells; second, we review how tumor cells rewind mitochondrial function for their oncogenic purpose via known or unknown mechanisms by key oncogenes or tumor suppressors; third, we go through reagents and strategies currently available targeting mitochondria when treating tumors. Recently, merging data suggest that slow cycling cancer cells/cancer stem cells have distinctive mitochondrial metabolism comparing to bulk tumor cells and mitochondria inhibitors seem to be promising to target them, which are resistant to traditional radio and chemotherapies. We thus discuss role of mitochondria in these cancer stem cells and summarize mitochondria as a target from different aspects. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

A Comparison of Doxorubicin-Resistant Colon Cancer LoVo and Leukemia HL60 Cells: Common Features, Different Underlying Mechanisms

“…Moreover, mitochondrial fission dependent on DRP1 is essential for stemness maintenance [55] and we have previously shown that LoVo-R are more staminal than LoVo-S [13]. It will be challenging to reprogram mitochondria in LoVo cells and investigate stemness, growth rate, invasiveness and sensitivity to anticancer drugs [56]. Turning to HL-60, no differences in the amounts of OPA1 and DRP1 were detected between sensitive or resistant cells.…”

Beyond the Warburg Effect: Oxidative and Glycolytic Phenotypes Coexist within the Metabolic Heterogeneity of Glioblastoma

“…Future directions in this field might entail a more precise molecular classification of tumor biopsies, expanding the comparison between gene expression subtypes and their metabolic milieu, and imaging of patients for improved, tailor-made therapeutics. Stratification and metabolic analysis will be crucial to discover malignancies that could benefit from adjuvant anti-glycolytic therapy [ 108 , 109 ], specific pathway inhibition (e.g., mitochondrial, glutamine and FAO inhibitors [ 110 , 111 , 112 ]) and tumors where, due to molecular rewiring, glycolysis inhibition with compensatory fuels might even be contraindicated [ 25 , 113 , 114 ].…”

Berberine Photo-Activation Potentiates Cytotoxicity in Human Astrocytoma Cells through Apoptosis Induction

“…Electron microscopy analyses documented that BBR and the combined treatment with photo-stimulation produced a marked damaged of mitochondria, with disrupted and discontinuous outer membranes and cristae. Again, the identification of an evident mitochondria vulnerability might be a promising direction for the generation of antitumor drug development [58].…”