Targeting mitochondria in the treatment of human cancer: a coordinated attack against cancer cell energy metabolism and signalling

Abstract

Mitochondria have major roles in bioenergetics and vital signalling of the mammalian cell. Consequently, these organelles have been implicated in the process of carcinogenesis, which includes alterations of cellular metabolism and cell death pathways. Multiple molecular routes of malignant transformation appear to result in the common ability of many tumours to take up large amounts of glucose. This metabolic twist has been explained by phenomena such as aerobic glycolysis and impaired mitochondrial function, and is linked to tumour growth potential via major cellular signalling pathways. This paper reviews the literature on central mechanisms through which energy metabolism merges with growth, proliferation and death signalling, which tend to include mitochondria at some level. These processes can potentially be targeted by pharmacological agents for therapeutic and chemosensitising purposes.

Keywords::

• aerobic glycolysis
• AMP-activated protein kinase
• bioenergetics
• chemotherapy
• hexokinase II
• hypoxia inducible factor 1-α
• mitochondria
• oxidative phosphorylation
• p53
• peroxisome proliferator activated receptor
• Warburg effect

Notes