Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
10.6
6.0
Journals
Antioxidants
Special Issues
Reactive Oxygen Species in Cancer Therapy
share announcement

Reactive Oxygen Species in Cancer Therapy

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: closed (15 February 2022) | Viewed by 10056

Special Issue Editor

Prof. Dr. Hirofumi Matsui

E-Mail
Guest Editor
Faculty of Medicine, University of Tsukuba, Ibaraki 305-0005, Japan
Interests: mitochondria; reactive oxygen species; neoplasm; chemotherapy; photodynamic therapy

Special Issue Information

Dear Colleagues,

Hyperthermia (HT) is a cancer treatment strategy. The difference in sensitivities becomes high at a low pH and, under nutritional deprivation, cancer tissues are more sensitive to heat than normal tissues. Because the effect of HT alone is not sufficient for cancer treatment, it is used in combination with conventional therapies, especially chemotherapy. The combination therapies not only exhibit synergistic effects but also have lower side effects because of the reduced dosages of drugs. The most important problem with chemotherapy is the drug resistance of cancer cells. It is known that resistant cells express transporters associated with altered drug permeability. Many anticancer drugs are excreted from the cells by the action of ATP-binding cassette (ABC) transporters. Some drug-resistant cancer cells, including cancer stem cells, overexpress ABC transporters and, therefore, they escape the cytotoxicity of anticancer drugs owing to insufficient intracellular drug concentrations. We have reported that HT can downregulate the expression of ABC transporter via an increase in mitochondrial reactive oxygen species (mitROS) production and then compound, which is thrown out via the ABC transporter, accumulating in an increase. As in other cases, to enhance the treatment of drug-resistance cancer cells, some researchers reported that competitive inhibitors can enhance the effect of anticancer drugs, because the efflux transporters of competitive inhibitor and anticancer drugs are the same. We considered whether the effect of anticancer drugs could be enhanced by regulating the expression of ABC transporters and using the competitive inhibitor, and demonstrated some investigations in this study.

We elucidated that HT can induce mitROS generation in cancer cells and enhanced porphyrin synthesis in cells treated with ALA. ALA is a precursor of porphrin, and porphyrin is a competitive inhibitor of anticancer drugs such as doxorubicin (DOX).  HT can downregurate ABCG2 expression and increase intracellular DOX accumulation. Moreover, the combination of HT and ALA treatment synergistically enhanced the cytotoxicity of DOX.

In conclusion, in the regulation of transporter expression by HT via the increase in mitROS production, in combination with ALA treatment used as a competitive inhibitor, the cytotoxic effect of DOX is enhanced. The increase in intracellular porphyrin accumulation after ALA uptake is a cancer-specific phenomenon; thus, competitive inhibition of anticancer drugs by ALA can result in lesser side effects for normal tissues. A combination of HT and chemotherapy has been evaluated in a clinical trial. The administration of ALA has no limitations in terms of clinical cure because it has no side effects; thus, in combination with HT, DOX and ALA could be very useful in breast cancer treatment in the future.

ALA could be very useful in breast cancer treatment in the future. In this Special Issue, we aim to collect original research papers regarding the following topics:

  1. Regulation of ABC transporter expression to accelerate the anticancer drug effect;
  2. Optimal competitive inhibitor to attenuate the drug resistance in cancer cells;
  3. Enhancement of anticancer drugs without side effects;
  4. The combination of chemotherapy and other treatment;
  5. Reactive Oxygen Species effect in chemotherapy.

Prof. Dr. Hirofumi Matsui
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • doxorubicin
  • 5-aminolevulinic acid
  • hyperthermia
  • mitochondrial reactive oxygen species.

Published Papers (3 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

19 pages, 3065 KiB  
Article
Oxidative Damage Induced by Phototoxic Pheophorbide a 17-Diethylene Glycol Ester Encapsulated in PLGA Nanoparticles
by Mariia R. Mollaeva, Elena Nikolskaya, Veronika Beganovskaya, Maria Sokol, Margarita Chirkina, Sergey Obydennyi, Dmitry Belykh, Olga Startseva, Murad D. Mollaev and Nikita Yabbarov
Antioxidants 2021, 10(12), 1985; https://doi.org/10.3390/antiox10121985 - 13 Dec 2021
Cited by 13 | Viewed by 2728
Abstract
Pheophorbide a 17-diethylene glycol ester (XL-8), is a promising high-active derivative of known photosensitizer chlorin e6 used in photodynamic therapy. However, high lipophilicity and poor tumor accumulation limit XL-8 therapeutic application. We developed a novel XL-8 loaded with poly(D,L-lactide-co-glycolide) nanoparticles using the single [...] Read more.
Pheophorbide a 17-diethylene glycol ester (XL-8), is a promising high-active derivative of known photosensitizer chlorin e6 used in photodynamic therapy. However, high lipophilicity and poor tumor accumulation limit XL-8 therapeutic application. We developed a novel XL-8 loaded with poly(D,L-lactide-co-glycolide) nanoparticles using the single emulsion-solvent evaporation method. The nanoparticles possessed high XL-8 loading content (4.6%) and encapsulation efficiency (87.7%) and a small size (182 ± 19 nm), and negative surface charge (−22.2 ± 3.8 mV) contributed to a specific intracellular accumulation. Sustained biphasic XL-8 release from nanoparticles enhanced the photosensitizer photostability upon irradiation that could potentially reduce the quantity of the drug applied. Additionally, the encapsulation of XL-8 in the polymer matrix preserved phototoxic activity of the payload. The nanoparticles displayed enhanced cellular internalization. Flow cytometry and confocal laser-scanning microscopy studies revealed rapid XL-8 loaded nanoparticles distribution throughout the cell and initiation of DNA damage, glutathione depletion, and lipid peroxidation via reactive oxygen species formation. The novel nanoformulated XL-8 simultaneously revealed a significant phototoxicity accompanied with enhanced photostability, in contrast with traditional photosensitizers, and demonstrated a great potential for further in vivo studies. Full article
(This article belongs to the Special Issue Reactive Oxygen Species in Cancer Therapy)
►▼ Show Figures

Graphical abstract

10 pages, 3541 KiB  
Article
The Cytotoxicity of Doxorubicin Can Be Accelerated by a Combination of Hyperthermia and 5-Aminolevulinic Acid
by Hiromi Kurokawa and Hirofumi Matsui
Antioxidants 2021, 10(10), 1531; https://doi.org/10.3390/antiox10101531 - 27 Sep 2021
Cited by 2 | Viewed by 1771
Abstract
Chemotherapy is cytotoxic to various cancer cells and as well as normal cells. Thus, treatments that demonstrate selective cytotoxicity for cancer cells are desired. The combination of chemotherapy and other cancer therapies can show synergic cytotoxicity, which may be a clue to the [...] Read more.
Chemotherapy is cytotoxic to various cancer cells and as well as normal cells. Thus, treatments that demonstrate selective cytotoxicity for cancer cells are desired. The combination of chemotherapy and other cancer therapies can show synergic cytotoxicity, which may be a clue to the nature of the involved cancer cellar-specific damage. We previously reported a phenomenon whereby mitochondrial reactive oxygen species (mitROS) regulate the expression transporters involved in anticancer drug transport and mitROS production is increased by hyperthermia. Moreover, the uptake of 5-aminolevulinic acid (ALA) was enhanced by the increase in mitROS production. In this study, we investigated whether the combination of hyperthermia and ALA can enhance the cytotoxicity of doxorubicin. MitROS production and ALA-derived porphyrin accumulation by hyperthermia (HT) were increased in a murine breast cancer cell line. The expression of solute carrier 15A1 (SLC15A1) upregulated and an ATP-binding cassette subfamily G member 2 (ABCG2) downregulated by HT. Since SLC15A1 is an accumulating transporter for ALA, while ABCG2 is a porphyrin efflux transporter, porphyrin accumulation was enhanced. ABCG2 is also a doxorubicin efflux transporter. Thus, ALA treatment accelerates the intracellular concentration of porphyrin, which acts as a competitive inhibitor of doxorubicin. Indeed, the amount of intracellular doxorubicin was increased by a combination of HT and ALA. The cytotoxicity of doxorubicin was also enhanced. This enhancement was observed in the human breast cancer cell line while it was not seen in normal cells. The combination of HT and ALA treatment can enhance the cancer-specific cytotoxicity of doxorubicin. Full article
(This article belongs to the Special Issue Reactive Oxygen Species in Cancer Therapy)
►▼ Show Figures

Figure 1

Review

Jump to: Research

40 pages, 835 KiB  
Review
Hyperthermia Treatment as a Promising Anti-Cancer Strategy: Therapeutic Targets, Perspective Mechanisms and Synergistic Combinations in Experimental Approaches
by Ga Yeong Yi, Min Ju Kim, Hyo In Kim, Jinbong Park and Seung Ho Baek
Antioxidants 2022, 11(4), 625; https://doi.org/10.3390/antiox11040625 - 24 Mar 2022
Cited by 26 | Viewed by 4900
Abstract
Despite recent developments in diagnosis and treatment options, cancer remains one of the most critical threats to health. Several anti-cancer therapies have been identified, but further research is needed to provide more treatment options that are safe and effective for cancer. Hyperthermia (HT) [...] Read more.
Despite recent developments in diagnosis and treatment options, cancer remains one of the most critical threats to health. Several anti-cancer therapies have been identified, but further research is needed to provide more treatment options that are safe and effective for cancer. Hyperthermia (HT) is a promising treatment strategy for cancer because of its safety and cost-effectiveness. This review summarizes studies on the anti-cancer effects of HT and the detailed mechanisms. In addition, combination therapies with anti-cancer drugs or natural products that can effectively overcome the limitations of HT are reviewed because HT may trigger protective events, such as an increase of heat shock proteins (HSPs). In the 115 reports included, the mechanisms related to apoptosis, cell cycle, reactive oxygen species, mitochondrial membrane potential, DNA damage, transcription factors and HSPs were considered important. This review shows that HT is an effective inducer of apoptosis. Moreover, the limitations of HT may be overcome using combined therapy with anti-cancer drugs or natural products. Therefore, appropriate combinations of such agents with HT will exert maximal effects to treat cancer. Full article
(This article belongs to the Special Issue Reactive Oxygen Species in Cancer Therapy)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-3
Back to TopTop