Tumor Biology

, Volume 36, Issue 8, pp 5715–5725 | Cite as

Mitochondrial targeted peptides for cancer therapy

  • Sadaf Farsinejad
  • Zohre Gheisary
  • Sanaz Ebrahimi Samani
  • Ali Mohammad Alizadeh
Review

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.

Keywords

Mitochondria Peptide Cancer Review 

Abbreviations

MTP

Mitochondrial targeted peptides

IMM

Inner mitochondrial membrane

IMS

Inner mitochondrial space

Cyt c

Cytochrome c

MOMP

Mitochondrial outer membrane permeabilization

AIF

Apoptosis-inducing factor

Smac

Second mitochondria-derived activator of caspase

mPTP

Mitochondrial permeability transition pore

ROS

Reactive oxygen species

VDAC

Voltage-dependent anion channels

ETC

Mitochondrial electron transport chain

BH

Bcl-2 homology

ER

Endoplasmic reticulum

SCLC

Small cell lung cancer

AML

Acute myeloid leukemia

CLL

Chronic lymphocytic leukemia

CML

Chronic myeloid leukemia

ALL

Acute lymphoblastic leukemia

HCC

Hepatocellular carcinoma

IP3

Inositol 1,4,5-trisphosphate

Notes

Acknowledgments

This study was supported by Tehran University of Medical Sciences (Grant Number: 25673).

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Sadaf Farsinejad
    • 1
  • Zohre Gheisary
    • 1
  • Sanaz Ebrahimi Samani
    • 1
  • Ali Mohammad Alizadeh
    • 1
  1. 1.Cancer Research CenterTehran University of Medical SciencesTehranIran

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