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Irradiation and Anti-cancer Therapies: Future and Challenges
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Irradiation and Anti-cancer Therapies: Future and Challenges

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 10516

Special Issue Editors

Prof. Dr. Dorota Wrześniok

E-Mail Website
Guest Editor
Department of Pharmaceutical Chemistry, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, Jagiellońska 4, 41-200 Sosnowiec, Poland
Interests: eumelanin; pyrrole-2,3,5-tricarboxylic acid; Auricularia auricula-judae
Special Issues, Collections and Topics in MDPI journals
Dr. Jakub Rok

E-Mail Website
Guest Editor
Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Jagiellońska 4, 41-200 Sosnowiec, Poland
Interests: lomefloxacin; melanoma; oxidative stress; DNA fragmentation; apoptosis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

The safety and efficacy of cancer therapy present a current and essential medical and scientific problem. The interdisciplinary nature of cancer research, as well as a wide scope of the studies, allow for the use and combination of knowledge and techniques from various fields of science, i.e., biophysics, pharmaceutical chemistry, cell biology, and molecular biology. As a result, we can improve our understanding and develop new methods of cancer treatment. They include different types and ranges of radiation, also in combination with anti-cancer drugs and photoactive substances.

A therapy with radiation has favorable clinical results and limited side effects on healthy tissues. It is assumed that about 50% of cancer patients receive radiotherapy. Apart from this method, the attention of scientists and clinicians focuses on other sources and types of radiation, including UV and visible light. Moreover, many ongoing studies are related to seeking new photosensitizers and adjuvant substances in photochemotherapy. In the face of clinical problems, all studies revealing the biochemical, molecular, and cellular basis of applied irradiation and combined therapies appear to be of a great importance and value. This Special Issue aims to present the potential perspectives of using the latest discoveries, as well as the physical, chemical, and biological effects that this has on irradiation-based cancer therapy.

Prof. Dr. Dorota Wrześniok
Dr. Jakub Rok
Guest Editors

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • cancer
  • irradiation
  • photosensitizer
  • photobiology
  • phototherapy
  • photodynamic therapy
  • radiobiology
  • free radicals
  • DNA damage
  • cell death
  • signaling pathway
  • targeted therapy
  • oxidative stress
  • cell cycle

Published Papers (5 papers)

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Research

14 pages, 6410 KiB  
Article
Tumor Radiosensitization by Gene Electrotransfer-Mediated Double Targeting of Tumor Vasculature
by Monika Savarin, Katarina Znidar, Gregor Sersa, Tilen Komel, Maja Cemazar and Urska Kamensek
Int. J. Mol. Sci. 2023, 24(3), 2755; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24032755 - 01 Feb 2023
Viewed by 1358
Abstract
Targeting the tumor vasculature through specific endothelial cell markers involved in different signaling pathways represents a promising tool for tumor radiosensitization. Two prominent targets are endoglin (CD105), a transforming growth factor β co-receptor, and the melanoma cell adhesion molecule (CD1046), present also on [...] Read more.
Targeting the tumor vasculature through specific endothelial cell markers involved in different signaling pathways represents a promising tool for tumor radiosensitization. Two prominent targets are endoglin (CD105), a transforming growth factor β co-receptor, and the melanoma cell adhesion molecule (CD1046), present also on many tumors. In our recent in vitro study, we constructed and evaluated a plasmid for simultaneous silencing of these two targets. In the current study, our aim was to explore the therapeutic potential of gene electrotransfer-mediated delivery of this new plasmid in vivo, and to elucidate the effects of combined therapy with tumor irradiation. The antitumor effect was evaluated by determination of tumor growth delay and proportion of tumor free mice in the syngeneic murine mammary adenocarcinoma tumor model TS/A. Histological analysis of tumors (vascularization, proliferation, hypoxia, necrosis, apoptosis and infiltration of immune cells) was performed to evaluate the therapeutic mechanisms. Additionally, potential activation of the immune response was evaluated by determining the induction of DNA sensor STING and selected pro-inflammatory cytokines using qRT-PCR. The results point to a significant radiosensitization and a good therapeutic potential of this gene therapy approach in an otherwise radioresistant and immunologically cold TS/A tumor model, making it a promising novel treatment modality for a wide range of tumors. Full article
(This article belongs to the Special Issue Irradiation and Anti-cancer Therapies: Future and Challenges)
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19 pages, 3616 KiB  
Article
The Assessment of the Phototoxic Action of Chlortetracycline and Doxycycline as a Potential Treatment of Melanotic Melanoma—Biochemical and Molecular Studies on COLO 829 and G-361 Cell Lines
by Jakub Rok, Zuzanna Rzepka, Klaudia Banach, Justyna Kowalska and Dorota Wrześniok
Int. J. Mol. Sci. 2023, 24(3), 2353; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24032353 - 25 Jan 2023
Cited by 3 | Viewed by 1743
Abstract
Melanoma is still one of the most dangerous cancers. New methods of treatment are sought due to its high aggressiveness and the relatively low effectiveness of therapies. Tetracyclines are drugs exhibiting anticancer activity. Previous studies have also shown their activity against melanoma cells. [...] Read more.
Melanoma is still one of the most dangerous cancers. New methods of treatment are sought due to its high aggressiveness and the relatively low effectiveness of therapies. Tetracyclines are drugs exhibiting anticancer activity. Previous studies have also shown their activity against melanoma cells. The possibility of tetracycline accumulation in pigmented tissues and the increase in their toxicity under the influence of UVA radiation creates the possibility of developing a new anti-melanoma therapy. This study aimed to analyze the phototoxic effect of doxycycline and chlortetracycline on melanotic melanoma cells COLO 829 and G-361. The results indicated that tetracycline-induced phototoxicity significantly decreased the number of live cells by cell cycle arrest as well as a decrease in cell viability. The simultaneous exposure of cells to drugs and UVA caused the depolarization of mitochondria as well as inducing oxidative stress and apoptosis. It was found that the combined treatment activated initiator and effector caspases, caused DNA fragmentation and elevated p53 level. Finally, it was concluded that doxycycline demonstrated a stronger cytotoxic and phototoxic effect. UVA irradiation of melanoma cells treated with doxycycline and chlortetracycline allows for the reduction of therapeutic drug concentrations and increases the effectiveness of tested tetracyclines. Full article
(This article belongs to the Special Issue Irradiation and Anti-cancer Therapies: Future and Challenges)
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19 pages, 7096 KiB  
Article
Low-Dose Near-Infrared Light-Activated Mitochondria-Targeting Photosensitizers for PDT Cancer Therapy
by Wenyu Wu Klingler, Nadine Giger, Lukas Schneider, Vipin Babu, Christiane König, Patrick Spielmann, Roland H. Wenger, Stefano Ferrari and Bernhard Spingler
Int. J. Mol. Sci. 2022, 23(17), 9525; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23179525 - 23 Aug 2022
Cited by 5 | Viewed by 2112
Abstract
Phthalocyanines (Pcs) are promising candidates for photodynamic therapy (PDT) due to their absorption in the phototherapeutic window. However, the highly aromatic Pc core leads to undesired aggregation and decreased reactive oxygen species (ROS) production. Therefore, short PEG chain functionalized A3B type [...] Read more.
Phthalocyanines (Pcs) are promising candidates for photodynamic therapy (PDT) due to their absorption in the phototherapeutic window. However, the highly aromatic Pc core leads to undesired aggregation and decreased reactive oxygen species (ROS) production. Therefore, short PEG chain functionalized A3B type asymmetric Pc photosensitizers (PSs) were designed in order to decrease aggregation and increase the aqueous solubility. Here we report the synthesis, characterization, optical properties, cellular localization, and cytotoxicity of three novel Pc-based agents (LC31, MLC31, and DMLC31Pt). The stepwise functionalization of the peripheral moieties has a strong effect on the distribution coefficient (logP), cellular uptake, and localization, as well as photocytotoxicity. Additional experiments have revealed that the presence of the malonic ester moiety in the reported agent series is indispensable in order to induce photocytotoxicity. The best-performing agent, MLC31, showed mitochondrial targeting and an impressive phototoxic index (p.i.) of 748 in the cisplatin-resistant A2780/CP70 cell line, after a low-dose irradiation of 6.95 J/cm2. This is the result of a high photocytotoxicity (IC50 = 157 nM) upon irradiation with near-infrared (NIR) light, and virtually no toxicity in the dark (IC50 = 117 μM). Photocytotoxicity was subsequently determined under hypoxic conditions. Additionally, a preliminarily pathway investigation of the mitochondrial membrane potential (MMP) disruption and induction of apoptosis by MLC31 was carried out. Our results underline how agent design involving both hydrophilic and lipophilic peripheral groups may serve as an effective way to improve the PDT efficiency of highly aromatic PSs for NIR light-mediated cancer therapy. Full article
(This article belongs to the Special Issue Irradiation and Anti-cancer Therapies: Future and Challenges)
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13 pages, 2295 KiB  
Article
Specific Targeting of Antiapoptotic Bcl-2 Proteins as a Radiosensitizing Approach in Solid Tumors
by Benjamin Sobol, Osama Azzam Nieto, Emily Lara Eberlein, Anna-Lena Scherr, Lars Ismail, Annika Kessler, Luisa Nader, Maximilian Schwab, Paula Hoffmeister, Nathalie Schmitt, Dirk Jäger, Stefan Welte, Katharina Seidensaal, Petros Christopoulos, Christoph Heilig, Katharina Kriegsmann, Stefan Fröhling, Mark Kriegsmann, Jochen Hess and Bruno Christian Köhler
Int. J. Mol. Sci. 2022, 23(14), 7850; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23147850 - 16 Jul 2022
Cited by 3 | Viewed by 2373
Abstract
Avoidance of therapy-induced apoptosis is a hallmark of acquired resistance towards radiotherapy. Thus, breaking resistance still challenges modern cancer therapy. The Bcl-2 protein family is known for its regulatory role in apoptosis signaling, making Bcl-2, Mcl-1 and Bcl-xL promising targets. This study [...] Read more.
Avoidance of therapy-induced apoptosis is a hallmark of acquired resistance towards radiotherapy. Thus, breaking resistance still challenges modern cancer therapy. The Bcl-2 protein family is known for its regulatory role in apoptosis signaling, making Bcl-2, Mcl-1 and Bcl-xL promising targets. This study evaluates the effects of highly specific inhibitors for Bcl-xL (WEHI-539), Bcl-2 (ABT-199) and Mcl-1 (S63845) as radiosensitizers. Covering a broad spectrum of solid tumors, Non-Small-Cell Lung Cancer (NSCLC), Head and Neck Squamous Cell Carcinoma (HNSCC) and synovial sarcoma cell lines were exposed to fractionated radiation as standard therapy with or without Bcl-2 protein inhibition. Protein expression was detected by Western blot and cell death was assessed by flow cytometry measuring apoptosis. In contrast to NSCLC, a high level of Bcl-xL and its upregulation during radiotherapy indicated radioresistance in HNSCC and synovial sarcoma. Radioresistant cell lines across all entities benefited synergistically from combined therapy with Bcl-xL inhibition and fractionated radiation. In NSCLC cell lines, Mcl-1 inhibition significantly augmented radiotherapy independent of the expression level. Our data suggest that among antiapoptotic Bcl-2 proteins, targeting Bcl-xL may break resistance to radiation in HNSCC, synovial sarcoma and NSCLC in vitro. In NSCLC, Mcl-1 might be a promising target that needs further investigation. Full article
(This article belongs to the Special Issue Irradiation and Anti-cancer Therapies: Future and Challenges)
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19 pages, 4052 KiB  
Article
Mechanisms of Resistance to Photodynamic Therapy (PDT) in Vulvar Cancer
by Beata Joanna Mossakowska, Somayeh Shahmoradi Ghahe, Dominik Cysewski, Anna Fabisiewicz, Barbara Tudek and Janusz Aleksander Siedlecki
Int. J. Mol. Sci. 2022, 23(8), 4117; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23084117 - 08 Apr 2022
Cited by 5 | Viewed by 2364
Abstract
Photodynamic therapy (PDT) is a valuable treatment method for vulvar intraepithelial neoplasia (VIN). It allows for the treatment of a multifocal disease with minimal tissue destruction. 5-Aminolevulinic acid (5-ALA) is the most commonly used prodrug, which is converted in the heme pathway to [...] Read more.
Photodynamic therapy (PDT) is a valuable treatment method for vulvar intraepithelial neoplasia (VIN). It allows for the treatment of a multifocal disease with minimal tissue destruction. 5-Aminolevulinic acid (5-ALA) is the most commonly used prodrug, which is converted in the heme pathway to protoporphyrin IX (PpIX), an actual photosensitizer (PS). Unfortunately, not all patients treated with PDT undergo complete remission. The main cause of their failure is resistance to anticancer therapy. In many cancers, resistance to various anticancer treatments is correlated with increased activity of the DNA repair protein apurinic/apyrimidinic endonuclease 1 (APE1). Enhanced activity of drug pumps may also affect the effectiveness of therapy. To investigate whether multidrug resistance mechanisms underlie PDT resistance in VIN, porphyrins were isolated from sensitive and resistant vulvar cancer cells and their culture media. APE1 activity was measured, and survival assay after PDT combined with APE1 inhibitor was performed. Our results revealed that resistant cells accumulated and effluxed less porphyrins than sensitive cells, and in response to PDT, resistant cells increased APE1 activity. Moreover, PDT combined with inhibition of APE1 significantly decreased the survival of PDT-resistant cells. This means that resistance to PDT in vulvar cancer may be the result of alterations in the heme synthesis pathway. Moreover, increased APE1 activity may be essential for the repair of PDT-mediated DNA damage, and inhibition of APE1 activity may increase the efficacy of PDT. Full article
(This article belongs to the Special Issue Irradiation and Anti-cancer Therapies: Future and Challenges)
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