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Biomolecules
Special Issues
Anticancer Platinum Drugs Update
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Anticancer Platinum Drugs Update

A special issue of Biomolecules (ISSN 2218-273X).

Deadline for manuscript submissions: closed (30 June 2019) | Viewed by 22155

Special Issue Editor

Prof. Dr. Giuliano Ciarimboli

E-Mail Website
Guest Editor
Experimental Nephrology, Department of Internal Medicine and Nephrology, Medical Clinic D, University Hospital Münster, 48149 Münster, Germany
Interests: organic cation transporters; regulation; interaction with drugs; interaction partners
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Following the serendipitous discovery of anticancer properties of cisplatin by Rosenberg, in 1972, clinical trials of cisplatin in human cancer patients were started. In 1978, cisplatin was first approved by the Food and Drug Administration (FDA) for treatment of testicular cancer and advanced ovarian and bladder cancer. Today, cisplatin is an important component of combination therapy of solid tumors, such as bladder, cervical, ovarian, lung, gastric, breast, and head and neck cancers. Importantly, chemotherapeutic treatment of testicular cancer with cisplatin is considered to be almost curative. Unfortunately, the success of cisplatin cancer therapy is limited by the development of resistance and of severe side effects, such as nephrotoxicity, ototoxicity, and peripheral neurotoxicity. These toxicities strongly decrease life quality in cancer survivors.

Cisplatin and the other platinum derivatives damage cancer cells by binding to the DNA and forming cross-links, which produce distortions in the double helix, affecting DNA transcription and replication and inducing cell apoptosis.

In the attempt to overcome resistance and to avoid the toxic side effects of cisplatin, several other platinum derivatives (e.g., carboplatin, oxaliplatin, nedaplatin, satraplatin, and phenanthriplatin) and application strategies have been developed and are still in development. Platinum derivatives are included in 50% of all chemotherapeutic protocols used in cancer treatment.

Today, cancer treatment is evolving toward personalized medicine, where chemotherapeutic treatment is combined with targeted medicines.

The aim of this special issue is to offer an update on the role of platinum drugs in modern cancer therapy based on the contributions of experts in this field.

Specifically, this Special Issue focusses on

a) the application of specific therapy schemes;
b) the elucidation of mechanisms which determine the development of resistance and the development of desired antitumor effects and of undesired side effects;
c) the development of new platinum drug formulations and the synthesis of new platinum derivatives.

Other ideas regarding platinum anticancer drugs are also welcome.

Prof. Dr. Giuliano Ciarimboli 
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. Biomolecules 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 2700 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

  • platinum anticancer agents
  • chemotherapy
  • solid tumors
  • resistance
  • side effects
  • toxicities
  • DNA cross-links
  • transport
  • drug formulations
  • life quality after cancer

Published Papers (6 papers)

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Editorial

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3 pages, 194 KiB  
Editorial
Anticancer Platinum Drugs Update
by Giuliano Ciarimboli
Biomolecules 2021, 11(11), 1637; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11111637 - 04 Nov 2021
Cited by 10 | Viewed by 1814
Abstract
The discovery of the anticancer properties of platinum derivatives by Rosenberg represents a milestone in the development of chemotherapeutic protocols for tumor treatment [...] Full article
(This article belongs to the Special Issue Anticancer Platinum Drugs Update)

Research

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16 pages, 1473 KiB  
Article
Effects of Single Nucleotide Polymorphism Ala270Ser (rs316019) on the Function and Regulation of hOCT2
by Dominik Frenzel, Christina Köppen, Oliver Bolle Bauer, Uwe Karst, Rita Schröter, Mladen V. Tzvetkov and Giuliano Ciarimboli
Biomolecules 2019, 9(10), 578; https://0-doi-org.brum.beds.ac.uk/10.3390/biom9100578 - 07 Oct 2019
Cited by 11 | Viewed by 2884
Abstract
The human organic cation transporter 2 (hOCT2) is highly expressed in proximal tubules of the kidneys, where it plays an important role in the secretion of organic cations. Since many drugs are organic cations, hOCT2 has relevant pharmacological implications. The hOCT2 gene is [...] Read more.
The human organic cation transporter 2 (hOCT2) is highly expressed in proximal tubules of the kidneys, where it plays an important role in the secretion of organic cations. Since many drugs are organic cations, hOCT2 has relevant pharmacological implications. The hOCT2 gene is polymorphic, and the nonsynonymous single nucleotide polymorphism (SNP) causing the substitution of alanine at position 270 of the protein sequence with serine (Ala270Ser) is present with high frequency in the human population. Therefore, Ala270Ser has potentially important pharmacologic consequences. Here, we analyzed the transport properties and rapid regulation of hOCT2 wildtype and hOCT2 Ala270Ser expressed in human embryonic kidney cells using real-time uptake measurements. Moreover, we compared the expression of hOCT2 in the plasma membrane determined by biotinylation experiments and the cellular transport and toxicity of cisplatin measured by inductively coupled plasma mass spectrometry and a viability test, respectively. The transport characteristics and regulation of the wildtype and mutated hOCT2 were very similar. Interestingly, a higher affinity of hOCT2 Ala270Ser for creatinine was observed. Compared with hOCT2 wildtype, the plasma membrane expression, cisplatin transport, and cisplatin-associated toxicity of hOCT2 Ala270Ser were significantly lower. In conclusion, these findings suggest that Ala270Ser has subtle but important effects on hOCT2 function, which are probably difficult to detect in studies with patients. Full article
(This article belongs to the Special Issue Anticancer Platinum Drugs Update)
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16 pages, 20835 KiB  
Article
Partial Surface Modification of Low Generation Polyamidoamine Dendrimers: Gaining Insight into their Potential for Improved Carboplatin Delivery
by Dai Hai Nguyen, Long Giang Bach, Diem-Huong Nguyen Tran, Van Du Cao, Thi Nhu Quynh Nguyen, Thi Thu Hong Le, Thach Thao Tran and Thai Thanh Hoang Thi
Biomolecules 2019, 9(6), 214; https://0-doi-org.brum.beds.ac.uk/10.3390/biom9060214 - 02 Jun 2019
Cited by 20 | Viewed by 3845
Abstract
Carboplatin (CAR) is a second generation platinum-based compound emerging as one of the most widely used anticancer drugs to treat a variety of tumors. In an attempt to address its dose-limiting toxicity and fast renal clearance, several delivery systems (DDSs) have been developed [...] Read more.
Carboplatin (CAR) is a second generation platinum-based compound emerging as one of the most widely used anticancer drugs to treat a variety of tumors. In an attempt to address its dose-limiting toxicity and fast renal clearance, several delivery systems (DDSs) have been developed for CAR. However, unsuitable size range and low loading capacity may limit their potential applications. In this study, PAMAM G3.0 dendrimer was prepared and partially surface modified with methoxypolyethylene glycol (mPEG) for the delivery of CAR. The CAR/PAMAM G3.0@mPEG was successfully obtained with a desirable size range and high entrapment efficiency, improving the limitations of previous CAR-loaded DDSs. Cytocompatibility of PAMAM G3.0@mPEG was also examined, indicating that the system could be safely used. Notably, an in vitro release test and cell viability assays against HeLa, A549, and MCF7 cell lines indicated that CAR/PAMAM G3.0@mPEG could provide a sustained release of CAR while fully retaining its bioactivity to suppress the proliferation of cancer cells. These obtained results provide insights into the potential of PAMAM G3.0@mPEG dendrimer as an efficient delivery system for the delivery of a drug that has strong side effects and fast renal clearance like CAR, which could be a promising approach for cancer treatment. Full article
(This article belongs to the Special Issue Anticancer Platinum Drugs Update)
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10 pages, 1603 KiB  
Article
Adsorption and Diffusion of Cisplatin Molecules in Nanoporous Materials: A Molecular Dynamics Study
by Marjan A. Nejad and Herbert M. Urbassek
Biomolecules 2019, 9(5), 204; https://0-doi-org.brum.beds.ac.uk/10.3390/biom9050204 - 27 May 2019
Cited by 11 | Viewed by 3691
Abstract
Using molecular dynamics simulations, the adsorption and diffusion of cisplatin drug molecules in nanopores is investigated for several inorganic materials. Three different materials are studied with widely-varying properties: metallic gold, covalent silicon, and silica. We found a strong influence of both the van [...] Read more.
Using molecular dynamics simulations, the adsorption and diffusion of cisplatin drug molecules in nanopores is investigated for several inorganic materials. Three different materials are studied with widely-varying properties: metallic gold, covalent silicon, and silica. We found a strong influence of both the van der Waals and the electrostatic interaction on the adsorption behavior on the pore walls, which in turn influence the diffusion coefficients. While van der Waals forces generally lead to a reduction of the diffusion coefficient, the fluctuations in the electrostatic energy induced by orientation changes of the cisplatin molecule were found to help desorb the molecule from the wall. Full article
(This article belongs to the Special Issue Anticancer Platinum Drugs Update)
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14 pages, 7921 KiB  
Article
[Pt(O,O′-acac)(γ-acac)(DMS)] Induces Autophagy in Caki-1 Renal Cancer Cells
by Giovanna Antonaci, Luca Giulio Cossa, Antonella Muscella, Carla Vetrugno, Sandra Angelica De Pascali, Francesco Paolo Fanizzi and Santo Marsigliante
Biomolecules 2019, 9(3), 92; https://0-doi-org.brum.beds.ac.uk/10.3390/biom9030092 - 06 Mar 2019
Cited by 6 | Viewed by 3396
Abstract
We have demonstrated the cytotoxic effects of [Pt(O,O′-acac)(γ-acac)(dimethyl sulfide (DMS))] on various immortalized cell lines, in primary cultures, and in murine xenograft models in vivo. Recently, we also showed that [Pt(O,O′-acac)(γ-acac)(DMS)] is able to kill [...] Read more.
We have demonstrated the cytotoxic effects of [Pt(O,O′-acac)(γ-acac)(dimethyl sulfide (DMS))] on various immortalized cell lines, in primary cultures, and in murine xenograft models in vivo. Recently, we also showed that [Pt(O,O′-acac)(γ-acac)(DMS)] is able to kill Caki-1 renal cells both in vivo and in vitro. In the present paper, apoptotic and autophagic effects of [Pt(O,O′-acac)(γ-acac)(DMS)] and cisplatin were studied and compared using Caki-1 cancerous renal cells. The effects of cisplatin include activation of caspases, proteolysis of enzyme poly ADP ribose polymerase (PARP), control of apoptosis modulators B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and BH3-interacting domain death agonist (Bid), and cell cycle arrest in G2/M phase. Conversely, [Pt(O,O′-acac)(γ-acac)(DMS)] did not induce caspase activation, nor chromatin condensation or DNA fragmentation. The effects of [Pt(O,O′-acac)(γ-acac)(DMS)] include microtubule-associated proteins 1A/1B light chain 3B (LC3)-I to LC3-II conversion, Beclin-1 and Atg-3, -4, and -5 increase, Bcl-2 decrease, and monodansylcadaverine accumulation in autophagic vacuoles. [Pt(O,O′-acac)(γ-acac)(DMS)] also modulated various kinases involved in intracellular transduction regulating cell fate. [Pt(O,O′-acac)(γ-acac)(DMS)] inhibited the phosphorylation of mammalian target of rapmycin (mTOR), p70S6K, and AKT, and increased the phosphorylation of c-Jun N-terminal kinase (JNK1/2), a kinase activity pattern consistent with autophagy induction. In conclusion, while in past reports the high cytotoxicity of [Pt(O,O′-acac)(γ-acac)(DMS)] was always attributed to its ability to trigger an apoptotic process, in this paper we show that Caki-1 cells die as a result of the induction of a strong autophagic process. Full article
(This article belongs to the Special Issue Anticancer Platinum Drugs Update)
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Review

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22 pages, 2467 KiB  
Review
Platinum Derivatives Effects on Anticancer Immune Response
by Cédric Rébé, Lucie Demontoux, Thomas Pilot and François Ghiringhelli
Biomolecules 2020, 10(1), 13; https://0-doi-org.brum.beds.ac.uk/10.3390/biom10010013 - 20 Dec 2019
Cited by 55 | Viewed by 5817
Abstract
Along with surgery and radiotherapy, chemotherapeutic agents belong to the therapeutic arsenal in cancer treatment. In addition to their direct cytotoxic effects, these agents also impact the host immune system, which might enhance or counteract their antitumor activity. The platinum derivative compounds family, [...] Read more.
Along with surgery and radiotherapy, chemotherapeutic agents belong to the therapeutic arsenal in cancer treatment. In addition to their direct cytotoxic effects, these agents also impact the host immune system, which might enhance or counteract their antitumor activity. The platinum derivative compounds family, mainly composed of carboplatin, cisplatin and oxaliplatin, belongs to the chemotherapeutical arsenal used in numerous cancer types. Here, we will focus on the effects of these molecules on antitumor immune response. These compounds can induce or not immunogenic cell death (ICD), and some strategies have been found to induce or further enhance it. They also regulate immune cells’ fate. Platinum derivatives can lead to their activation. Additionally, they can also dampen immune cells by selective killing or inhibiting their activity, particularly by modulating immune checkpoints’ expression. Full article
(This article belongs to the Special Issue Anticancer Platinum Drugs Update)
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