Table 1.
Naturally occurring and synthetic fatty acids and other lipids: mitochondrial actions of potential value in cancer chemotherapy
| Fatty acid derivative | Mitochondrial actions | Pathways effected | Function | References |
|---|---|---|---|---|
| Butyric acid | Dissipation of the mitochondrial membrane potential (ΔΨ) | Caspase-3 activation | ↑Apoptosis Growth arrest | Heerdt et al. (1998) Milovic et al. (2000) |
| Bromo-analogues of butyric and propionic acids | ↑ROS, DNA damage | ↑Apoptosis | Milovic et al. (2000) | |
| Palmitic acid | ↓Mitochondrial membrane ΔΨ, cytochrome c release | ↑Apoptosis ↑Cell death | Merrill and Jones (1990) Schlame et al. (2000) Ostrander et al. (2001) | |
| 13-Methyltetradecanoic acid | Disrupted mitochondrial integrity and caused dysfunction, cytochrome c release | ↑Bax, ↓Bcl-2 Caspase-3 activation ↓pAkt ↑p38 and JNK MAPK | ↑Apoptosis Growth inhibition | Yang et al. (2000) Wongtangtintharn et al. (2005) Lin et al. (2012) |
| Arachidonic acid-derived PGE2 | ↑EGFR/ERK MAPK ↑PI3K/Akt | ↑Survival ↑Proliferation | Chen et al. (2009) | |
| Eicosapentaenoic acid (EPA) | ↑ATP glycolysis, ↑ROS, ↓mitochondrial membrane ΔΨ | Caspase-3 activation PKC inhibition, ↓Bcl-2 | ↑Apoptosis Growth inhibition | Denys et al. (2005) Colquhoun (2009) |
| EPA-derived epoxides | p38 MAPK | ↑Apoptosis Growth inhibition | Cui et al. (2011) | |
| Docosahexaenoic acid | PKC inhibition, ↓Bcl-2 | ↑Apoptosis | Denys et al. (2005) | |
| CLA | ↓DNA synthesis | ↓Bcl-2, ↓PI3K/Akt | ↑Apoptosis ↓Proliferation | Ip et al. (1999) Ip et al. (2000) Kim et al. (2002) |
| Jacaric acid | ↑ROS | ↓Bcl-2, caspase-3,-8 and-9 activation, PARP cleavage | ↑Apoptosis (intrinsic and/or extrinsic pathways) | Shinohara et al. (2012) Gasmi and Sanderson (2013) |
| α-Eleostearic acid | ↓Mitochondrial membrane ΔΨ, ↑DNA fragmentation ↑lipid peroxidation | ↑Apoptosis | Tsuzuki et al. (2004), Grossmann et al. (2009) | |
| Vaccenic acid | ↑DNA fragmentation | Growth inhibition ↓Cytosolic glutathione ↑Cell death | Miller et al. (2003) | |
| Punicic acid | Disrupted the mitochondrial membrane ΔΨ, ↑DNA fragmentation, ↑lipid peroxidation | Caspase-3 and-9 activation ↓Bcl-2 (decreased Bcl-2:Bax ratio) ↓pAkt | ↑Apoptosis | Grossmann et al. (2010), Gasmi and Sanderson (2010) |
| Tetradecylthioacetic acid | ↑Mitochondrial proliferation, ↑oxidative stress, ↑ROS | Caspase-3 activation PARP cleavage | ↑Apoptosis ↓Proliferation | Tronstad et al. (2001) Lin et al. (2012) Tronstad et al. (2003) |
| Jasmonates | Cytochrome c release, membrane depolarization, swelling of mitochondria, ↓ATP | ↑Cell death | Fingrut and Flescher (2002) Rotem et al. (2005) Fingrut et al. (2005) Heyfets and Flescher (2007) Goldin et al. (2007) | |
| EETs | ↑EGFR/ERK ↑PI3K/Akt | ↑Survival ↑Proliferation | Chen et al. (2009) | |
| HETEs and downstream LTs | Inhibition of 5-LOX depleted mitochondrial glutathione and ↑lipid peroxidation | ↑apoptotic Bcl-2 family proteins | ↑Survival Enhanced growth | Ghosh and Myers (1998) Avis et al. (2001) Hoque et al. (2005) |
| Short chain ceramides | Cytochrome c release, ↓mitochondrial membrane ΔΨ, ↑ROS | Caspase-3 activation, ↓Bcl-2: Bax ratio, ↑p38 and JNK MAPK phosphorylation, PARP | ↑Apoptosis | Fillet et al. (2003) Flowers et al. (2012) |
| Anandamide and N-acylethanolamines | ↑Permeability of inner mitochondrial membrane, ↑↓lipid peroxidation*, energetic and permeability transition alterations, Ca2+ overload and PTP modulation | ↑↓Apoptosis ↑↓proliferation | Epps et al. (1982) Gulaya et al. (1993) Schwarz et al. (1994) De Petrocellis et al. (1998) Maccarrone et al. (2000) Sarker et al. (2000) Wasilewski et al. (2004) | |
| Cardiolipin | Involved in ROS-promoted cytochrome c release | Membrane targeting of Bid, activation of Bax | ↑Apoptosis | Kuwana et al. (2002) |
| Perifosine | ↑Cytochrome c release, mitochondrial oxidative phosphorylation disruption, induction of permeability transition | Akt inhibition Caspase-3,-8 and-9 activation ↑JNK MAPK translocation | ↑Apoptosis | Kondapaka et al. (2003) Nieto-Miguel et al. (2006) Chiarini et al. (2008) Burgeiro et al. (2013) |
| Edelfosine | Mitochondrial dysfunction via multiple mechanisms Altered mitochondrial membrane ΔΨ, ↑DNA fragmentation, ↑ROS | Caspase-3 activation PARP | ↑Apoptosis | Cabaner et al. (1999) Gajate et al. (2000) Mollinedo et al. (2011) |
| Isopropylaminopropanol derivatives (C16:0 and C18:1) | Inhibition of multiple pro-survival kinases | Growth inhibition | Cao et al. (2013) |
*
Dependent on fatty acid chain length and saturation.