Friend or Foe? Mitochondria as a Pharmacological Target in Cancer Treatment

Abstract

Mitochondria have acquired numerous functions over the course of evolution, such as those involved in controlling energy production, cellular metabolism, cell survival, apoptosis and autophagy within host cells. Tumor cells can develop defects in mitochondrial function, presenting a potential strategy for designing selective anticancer therapies. Therefore, cancer has been the main focus of recent research to uncover possible mitochondrial targets for therapeutic benefit. This comprehensive review covers not only the recent discoveries of the roles of mitochondria in cancer development, progression and therapeutic implications but also the findings regarding emerging mitochondrial therapeutic targets and mitochondria-targeted agents. Current challenges and future directions for developments and applications of mitochondrial-targeted therapeutics are also discussed.

Triple Fluorescence staining to Evaluate Mechanism-based Apoptosis following Chemotherapeutic and Targeted Anti-cancer Drugs in Live Tumor Cells

“…As an energy-dependent process, a distinctive feature of apoptosis is the interference of normal mitochondrial function, and mitochondria-dependent intrinsic signaling pathways are recognized as a component of apoptosis 3 , hence targeting mitochondria in cancer cells has been considered as an attractive therapeutic strategy 4,5 . Compromised mitochondrial (trans)membrane potential (ΔΨm) and its collapse lead to the opening of mitochondrial permeability transition pores, and the subsequent release of cytochrome C in the cytosol, which in turn initiates penultimate downstream events in the apoptotic cascade of caspases.…”

Cancer Cell Metabolism: Implications for X-ray and Particle Radiation Therapy

“…Metabolic reprogramming in cancer cells was originally attributed to impaired mitochondrial activity but can occur by other means such as increased glycolytic enzyme expression following oncogene activation. Cancer cells can be induced to return to oxidative phosphorylation, and targeting mitochondria with this goal is being actively explored as a new approach to cancer therapy [60]. Accumulative data have shown that the metabolic switch towards aerobic glycolysis and lactate production represents an advantage for tumor development and invasion, and might be the result of clonal selection in progressive malignancies.…”

Features of Redox Regulation in Tumor Cells

“…тенденцию большинства раковых клеток производить энергию преимущественно с помощью анаэробного гликолиза с последующим образованием молочной кислоты [42]. Во многих исследованиях показано, что усиление продукции АКМ митохондриями активирует аутофагию [58], индуцирует выход ионов кальция из митохондрий и эндоплазматического ретикулума [46], посредством окисления киназы ASK1 (apoptosis signaling kinase 1) ингибирует апоптоз [35], повышает радио-и химиорезистентность опухолевых клеток [34]. Одним из важных механизмов уменьшения содержания митохондрий и генерации АКМ является митофагия.…”