The transformation of normal cells to the cancerous stage involves multiple genetic changes or mutations leading to hyperproliferation, resistance to apoptosis, and evasion of the host immune system. However, to accomplish hyperproliferation,
cancer cells undergo profound metabolic reprogramming including oxidative glycolysis and acidification of the cytoplasm, leading to hyperpolarization of the mitochondrial membrane. The majority of
drug development research in the past has focused on targeting DNA replication, repair, and
tubulin polymerization to induce apoptosis in
cancer cells. Unfortunately, these are not
cancer-selective targets. Recently, researchers have started focusing on metabolic, mitochondrial, and oxidative stress vulnerabilities of
cancer cells that can be exploited as selective targets for inducing
cancer cell death. Indeed, the hyperpolarization of mitochondrial membranes in
cancer cells can lead to selective importing of mitocans that can induce apoptotic effects. Herein, we will discuss recent mitochondrial-selective anticancer compounds (mitocans) that have shown selective toxicity against
cancer cells. Increased oxidative stress has also been shown to be very effective in selectively inducing cell death in
cancer cells. This oxidative stress could lead to
mitochondrial dysfunction, which in turn will produce more
reactive oxygen species (ROS). This creates a vicious cycle of
mitochondrial dysfunction and ROS production, irreversibly leading to cell suicide. We will also explore the possibility of combining these compounds to sensitize
cancer cells to the conventional
anticancer agents. Mitocans in combination with selective oxidative-stress producing agents could be very effective anticancer treatments with minimal effect on healthy cells.