Mitochondrial Delivery of Doxorubicin Using MITO-Porter Kills Drug-Resistant Renal Cancer Cells via Mitochondrial Toxicity

Yamada, Yuma; Munechika, Reina; Kawamura, Eriko; Sakurai, Yasuhisa; Sato, Yusuke; Harashima, Hideyoshi

doi:10.1016/j.xphs.2017.04.058

Cited by 26 publications

(19 citation statements)

References 25 publications

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“…The combination of a highly fusogenic lipid, 1,2-dioleoyl-sn-glycero-3-phosphatidyl ethanolamine (DOPE) and a cell-penetrating peptide, octaarginine (R8) plays an essential role in the cell internalization process via macropinocytosis, endosomal escape, and mitochondrial accumulation [19]. For mitochondrial targeting cancer therapy, the MITO-Porter system has been used to significantly improve the antitumor activity of an aminoglycoside drug against HeLa cells and an anthracycline compound toward doxorubicin (DOX) -resistant renal cancer cells [47,48]. We are currently developing a novel mitochondrial targeting PDT system consisting of a newly synthesized porphyrin-type PS, namely rTPA, that will be used in combination with the MITO-Porter system.…”

Section: Validation Of Cancer Therapeutic Strategy Using Mito-porter mentioning

confidence: 99%

Therapeutic Strategies for Regulating Mitochondrial Oxidative Stress

et al. 2020

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There have been many reports on the relationship between mitochondrial oxidative stress and various types of diseases. This review covers mitochondrial targeting photodynamic therapy and photothermal therapy as a therapeutic strategy for inducing mitochondrial oxidative stress. We also discuss other mitochondrial targeting phototherapeutic methods. In addition, we discuss anti-oxidant therapy by a mitochondrial drug delivery system (DDS) as a therapeutic strategy for suppressing oxidative stress. We also describe cell therapy for reducing oxidative stress in mitochondria. Finally, we discuss the possibilities and problems associated with clinical applications of mitochondrial DDS to regulate mitochondrial oxidative stress.Biomolecules 2020, 10, 83 2 of 23 Parkinson's and Alzheimer's diseases, by the direct neutralization of ROS and by suppressing inflammation [5,6]. Furthermore, CoQ 10 , a potent ubiquinone antioxidant, has been reported to show significant protective effects on mitochondria of the pancreatic beta cells during the oxidative stress induced by the chronic use of tacrolimus [7]. Due to the highly hydrophobic characteristics and the fact that most of the antioxidant molecules accumulate in a nonspecific manner, a high dose is needed to obtain the desired effects. Thus, the selective delivery of this compound would be expected to further strengthen its effectivity.In the context of cancer therapy, mitochondrial ROS were found to play an important role as a signaling molecule in controlling cell proliferation by virtue of its ability to regulate the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway [8]. Moreover, antioxidant activity, such as GSH and thioredoxin, was also reported to be essential for the initiation of and the progression of cancer. Inhibition of the antioxidant activity resulted in a significant reduction in tumor progression and metastasis [9][10][11]. These findings suggest that cancer cells are maintained under conditions of ROS stress and that antioxidant supplementation may be irrelevant for cancer therapy [12][13][14]. However, ROS interact with several major biologically active molecules such as proteins, lipids, and nucleic acids, leading to irreversible oxidative damage and the further induction of lethal effects for the cells. Therefore, promoting ROS production could be a promising strategy for treating tumors. There are numerous methods that can be employed to promote ROS levels in cancers, i.e., depleting or inhibiting antioxidant activity [15,16] and inhibiting the mitochondrial respiratory system [17], and producing an excessive amount of ROS through photochemical reactions. The latter effort shows a high selectivity for tumor cells, making it more encouraging in contrast to other efforts.This review focuses on therapeutic strategies for regulating mitochondrial oxidative stress. The main theme includes therapeutic strategies designed to induce oxidative stress and suppress mitochondrial oxidative stress (Figure 1). As ...

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Section: Validation Of Cancer Therapeutic Strategy Using Mito-porter mentioning

confidence: 99%

Therapeutic Strategies for Regulating Mitochondrial Oxidative Stress

et al. 2020

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“…Biocompatible molecules can be transported in different ways, including delivery of the compound from the extracellular space to the cytosol, targeting of the mitochondria, and mitochondrial delivery by membrane fusion. Yamada et al (364) have shown the MITO-Porter system to be an excellent carrier for mitochondrial delivery of a cytotoxic agent, which represents a possible therapeutic strategy for treating drug-resistant cancers.…”

Section: Type 2 Diabetes and New Therapeutic Targetsmentioning

confidence: 99%

Mitochondria, the NLRP3 Inflammasome, and Sirtuins in Type 2 Diabetes: New Therapeutic TargetsReviewing Editors:Markus Bachschmid, Dylan Burger, Vittorio Calabrese, Amadou Camara, Lukas Kubala, Giuseppe Poli, and Chandan K. Sen

Rovira‐Llopis

Apostolova

Bañuls

et al. 2018

Antioxidants & Redox Signaling

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In this review article, we attempt to provide an overview of the existing literature concerning the crosstalk between mitochondrial impairment and the inflammasome, with particular attention to cellular and mitochondrial redox metabolism and the potential role of the NLRP3 inflammasome and sirtuins in the pathogenesis of type 2 diabetes. In addition, we discuss potential targets for therapeutic intervention based on these molecular interactions. Antioxid. Redox Signal. 29, 749-791.

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“…The anthracyline causes mitochondrial dysfunction, e.g., displacing α-enolase from mitochondria [30]. ATP synthesis is decreased in both the cytosol and mitochondria by DOX [90].…”

Section: Doxorubicin's Effect On Myocardial Energy Metabolismmentioning

confidence: 99%

Mitochondrial Dysfunction Associated with Doxorubicin

Güven¹,

Sevgiler²,

Taşkın³

2018

Mitochondrial Diseases

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Cancer prevalence is scaling up each year. Anthracycline groups are still the best chemotherapeutic agent. The most popular anticancer drug in the group is doxorubicin (DOX). Unfortunately, DOX has potent toxicity on noncancerous tissues, e.g., heart, kidneys, etc. However, it is well documented that the severest toxicity of the drug affects heart tissue. Of course, some reasons have been suggested why and/or how the heart is so vulnerable to toxicity. The primary mechanism responsible for DOX's cardiospecific toxicity remains unidentified so far; however, mitochondrial dysfunction induced by DOX is now considered one of the leading reasons for DOX's toxicities and undesired side effects. Mitochondrial reactive oxygen production in the heart is a significant contributor to developing mitochondrial dysfunction-exposed DOX based on a variety of evidence. The objective of this review chapter is to critically evaluate and highlight the role of mitochondria in the development of DOX-induced cardiotoxicity. TurkeyMitochondrial Dysfunction Associated with Doxorubicin http://dx.doi.org/10.5772/intechopen.80284 353

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Mitochondrial Delivery of Doxorubicin Using MITO-Porter Kills Drug-Resistant Renal Cancer Cells via Mitochondrial Toxicity

Cited by 26 publications

References 25 publications

Therapeutic Strategies for Regulating Mitochondrial Oxidative Stress

Therapeutic Strategies for Regulating Mitochondrial Oxidative Stress

Mitochondria, the NLRP3 Inflammasome, and Sirtuins in Type 2 Diabetes: New Therapeutic TargetsReviewing Editors:Markus Bachschmid, Dylan Burger, Vittorio Calabrese, Amadou Camara, Lukas Kubala, Giuseppe Poli, and Chandan K. Sen

Mitochondrial Dysfunction Associated with Doxorubicin

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