Mitochondrial targeted peptides for cancer therapy

Abstract

Mitochondria are a key pharmacological target in all cancer cells, since the structure and function of this organelle is different between healthy and malignant cells. Oxidative damage, disruption of mitochondrial ATP synthesis, calcium dyshomeostasis, mtDNA damage, and induction of the mitochondrial outer membrane permeabilization (MOMP) lead to the mitochondrial dysfunctionality and increase the probability of the programmed cell death or apoptosis. A variety of the signaling pathways have been developed to promote cell death including overexpression of pro-apoptotic members of Bcl-2 family, overloaded calcium, and elevated reactive oxygen species (ROS) play a key role in the promoting mitochondrial cytochrome c release through MOMP and eventually leads to cell death. There are a wide range of the therapeutic-based peptide drugs, known mitochondrial targeted peptides (MTPs), which specifically target mitochondrial pathways into death. They have prominent advantages such as low toxicity, high specificity, and easy to synthesis. Some of these therapeutic peptides have shown to increased the clinical activity alone or in combination with other agents. In this review, we will outline the biological properties of MTPs for cancer therapy. Understanding the molecular mechanisms and signaling pathways controlling cell death by MTPs can be critical for the development of the therapeutic strategies for cancer patients that would be valuable for researchers in both fields of molecular and clinical oncology.

Oxytocin mediates the beneficial effects of the exercise training on breast cancer

“…If the expression of Bax becomes greater than that of Bcl2, cell apoptosis is induced; otherwise, the cell survives (Oltval et al 1993;Barnard et al 2007). Therefore, a therapeutic approach is to inhibit Bcl2 family proteins, and the targeting of anti-apoptotic Bcl2 proteins can promote cell death (Farsinejad et al 2015). In our experiment, the groups that showed a greater ratio of Bax to Bcl2 may indicate more caspase-3 expression and, consequently, cell apoptosis.…”

“…Therefore, a therapeutic approach is to inhibit Bcl2 family proteins, and the targeting of anti‐apoptotic Bcl2 proteins can promote cell death (Farsinejad et al . ). In our experiment, the groups that showed a greater ratio of Bax to Bcl2 may indicate more caspase‐3 expression and, consequently, cell apoptosis.…”

Sinularin induces DNA damage, G2/M phase arrest, and apoptosis in human hepatocellular carcinoma cells

“…Given DNA damage usually comes along with oxidative stress and that reactive oxygen species (ROS) could be involved in leading to the mitochondria outer membrane permeabilization (MOMP) [23, 24], it is possible that sinularin induced oxidative DNA damage as well. We measured the ROS levels by using the fluorescent probe DCFDA after sinularin treatment with HCC, but there were no significant changes observed between sinularin-treated cells and untreated cells, suggesting that sinularin-induced DNA damage and cytotoxicity is not associated with the generation of ROS in human HepG2 cells (data not shown).…”

Self-assembly of mitochondria-specific peptide amphiphiles amplifying lung cancer cell death through targeting the VDAC1–hexokinase-II complex

“…Cancer cell mitochondria are recognized as important targets for inhibition of the cancer progression in anti-cancer therapies. [1][2][3] They currently underlie new drug developments, which will complement the existing therapies for cancer cells killing and cancer elimination. [4][5][6][7][8][9][10][11][12] The mitochondrial-targeting anti-cancer mechanisms include the activation of mitochondria-mediated apoptotic pathways via voltagedependent-anion-channel (VDAC) targeting agents or electron transport/respiratory chain blockers, [13][14][15] the increased induction of reactive oxygen species (ROS), 16,17 the inhibition of the Bcl-2 anti-apoptotic family of proteins, 18 the activation of the mitochondrial membrane permeability transition pore protein subunits, 19,20 the mtDNA targeting in cancer cells, 19 and treatments involving mitochondrial destabilization, mitochondrial membrane permeabilization, 21 mitochondrial fission and massive mitochondrial fragmentation using lipophilic cations targeting the inner membrane.…”