Drugs targeting mitochondrial functions to control tumor cell growth

α-Tocopheryl succinate induces apoptosis by targeting ubiquinone-binding sites in mitochondrial respiratory complex II

“…Although anti-cancer drugs have been described that may target the UbQ sites on the oxidoreductase complexes along the mitochondrial respiratory chain to increase cellular ROS levels and activate apoptosis (Dias and Bailly, 2005;Hall, 2005;Le et al, 2007), a-TOS has an additional feature in that it also disrupts the anti-apoptotic function of Bcl-2 and Bcl-x L by blocking their BH3-binding domain (Shiau et al, 2006). Hence, a-TOS may prove superior for inducing cancer cell death because of its dual action on two important targets, Q P and Q D sites of CII, and the Bcl-2 family proteins, promoting the induction of mitochondrially mediated apoptosis.…”

Trichosanthin induced apoptosis in HL-60 cells via mitochondrial and endoplasmic reticulum stress signaling pathways

“…Central to this suicidal program is a cascade of caspases with caspase-3 being one of the key executioners which in turn are cleaved/activated by various initiator caspases. It is well accepted that in mammalian cells, there are two major pathways involved in apoptosis: the mitochondria-initiated intrinsic pathway and the death receptor-triggered extrinsic pathway [7][8][9]. For the former, proapoptotic signals provoke the release of cytochrome c from the mitochondrial intermembrane space into the cytosol, which forms a complex with Apaf-1 and dATP known as apoptosome and triggers caspase-9 activation.…”

“…For the former, proapoptotic signals provoke the release of cytochrome c from the mitochondrial intermembrane space into the cytosol, which forms a complex with Apaf-1 and dATP known as apoptosome and triggers caspase-9 activation. The activation of caspase-9 leads to the activation of the executioner caspases, such as caspase-3, -6, -7, which triggers a series of apoptotic events and eventually cell death [7,10,11]. The extrinsic pathway begins with a death receptor, such as Fas.…”

Mitochondria as a pharmacological target: Magnum overview

“…This clinical potential can be affirmed by the large number of articles associated with these types of drugs (Table 1) (34)(35)(36). Generally, authors classify these drugs according to the mitochondrial site of action (35)(36)(37)60), but these compounds, called mitocans, are also catalogued into nine groups based on the site of action of the individual agents from the surface of the outer mitochondrial membrane to the matrix (38,39). They are also sometimes divided based on their delivery method to the mitochondria (61,62).…”

“…Strategies to induce this effect typically involve direct action against the PTP protein complex or indirect action via depleting endogenous inhibitors of PTP or increasing calcium ions and ROS in the cytoplasm. In anticancer therapeutic approaches, various PTP complex inhibitors are used, including: 1) adenine nucleotide translocase modulators such as bongkrekic acid, GSAO (4-[N-[S-glutathionylacetyl]amino] phenylarsenoxide), PENAO (4-(N-(Spenicillaminylacetyl) amino) phenylarsonous acid), betulinic acid, lonidamide, clotrane, and CD437; 2) benzodiazepine receptor modulators such as PK11195 and Ro-54846; 3) voltage-dependent ion channel modulators such as arsenic trioxide; 4) cyclophilin D-affecting drugs such as cyclosporin A and sanglipherin A; 5) creatine kinase modulators such as creatine and cyclocreatine; and 6) hexokinase modulators such as glucose and glucose-6-phosphate (36,39). GSAO and PENAO are tumor-metabolism inhibitors that target adenine nucleotide translocase (ANT) of the inner-mitochondrial membrane.…”