Selective Integrin Ligands Promote Cell Internalization of the Antineoplastic Agent Fluorouracil

SummaryHydroxyurea (HU) is usually a well tolerated antineoplastic agent and is commonly used in the treatment of chronic myeloproliferative diseases. Dermatological side effects are frequently seen in patients receiving longterm HU therapy. Cutaneous ulcers have been reported occasionally.We report on four patients with cutaneous ulcers whilst on long-term hydroxyurea therapy for myeloproliferative diseases. In all patients we were able to reduce the dose, or stop HU altogether and their ulcers markedly improved. Our observations suggest that cutaneous ulcers should be considered as possible side effect of long-term HU therapy and healing of the ulcers can be achieved not only by cessation of the HU treatment, but also by reducing the dose of hydroxyurea for a limited time.

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The Anticancer Drug Ellipticine is an Inducer of Rat NAD(P)H:Quinone Oxidoreductase

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc20071350 ◽

2007 ◽

Vol 72 (10) ◽

pp. 1350-1364 ◽

Cited By ~ 1

Author(s):

Marie Stiborová ◽

Helena Dračínská ◽

Dagmar Aimová ◽

Petr Hodek ◽

Jiří Hudeček ◽

...

Keyword(s):

Polymerase Chain Reaction ◽

Enzymatic Activity ◽

Wistar Rats ◽

Antineoplastic Agent ◽

Chain Reaction ◽

Potent Inducer ◽

Male Wistar Rats ◽

Polymerase Chain ◽

Dt Diaphorase ◽

Rat Livers

The antineoplastic agent ellipticine was investigated for its ability to induce the biotransformation enzyme NAD(P)H:quinone oxidoreductase (DT-diaphorase, EC 1.6.99.2) in male Wistar rats. Using the real-time polymerase chain reaction, the levels of NAD(P)H:quinone oxidoreductase mRNA were determined in livers, kidneys and lungs of rats treated intraperitoneally with ellipticine (40 mg/kg body weight) and of control (untreated) rats. Cytosolic fractions were isolated from the same tissues of control and ellipticine-treated rats and tested for NAD(P)H:quinone oxidoreductase protein expression and its enzymatic activity. The results demonstrate that ellipticine is a potent inducer of NAD(P)H:quinone oxidoreductase in rat livers and kidneys, while no induction of this enzyme was detectable in rat lungs. The increase in levels of NAD(P)H:quinone oxidoreductase mRNA correlates with the increase in expression of its protein and enzymatic activity, measured with menadione and 3-nitrobenzanthrone as substrates. The results, the identification of the potential of ellipticine to induce NAD(P)H:quinone oxidoreductase, suggest that this drug is capable of modulating biological efficiencies of the toxicants and/or drugs that are reductively metabolized by this enzyme.

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Design, Syntheses, and Bioevaluations of Some Novel N2-Acryloylbenzohydrazides as Chemostimulants and Cytotoxic Agents

Medicines ◽

10.3390/medicines8060027 ◽

2021 ◽

Vol 8 (6) ◽

pp. 27

Author(s):

Kinjal Lakhani ◽

Edgar A. Borrego ◽

Karla G. Cano ◽

Jonathan R. Dimmock ◽

Renato J. Aguilera ◽

...

Keyword(s):

Antineoplastic Agent ◽

Cytotoxic Agents ◽

Breast Cancer Cell Lines ◽

Molecular Features ◽

In Series ◽

Hct 116 ◽

Related Series ◽

Hct 116 Cells ◽

Related Compounds ◽

Mcf 7

A series of novel N2-acryloylhydrazides 1a–m and a related series of compounds 6a–c were prepared as potential chemostimulants. In general, these compounds are cytotoxic to human HCT 116 colon cancer cells, as well as human MCF-7 and MDA-MB-231 breast cancer cell lines. A representative compound N1-(3,4-dimethoxyphenylcarbonyl)-N2-acryloylhydrazine 1m sensitized HCT 116 cells to the potent antineoplastic agent 3,5-bis(benzylidene)-4-piperidone 2a, and also to 5-fluorouracil. A series of compounds was prepared that incorporated some of the molecular features of 2a and related compounds with various N2-acryloylhydrazides in series 1. These compounds are potent cytotoxins. Two modes of action of representative compounds are the lowering of mitochondrial membrane potential and increasing the concentration of reactive oxygen species.

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Phytochemical and Biological Evaluation of a Newly Designed Nutraceutical Self-Nanoemulsifying Self-Nanosuspension for Protection and Treatment of Cisplatin Induced Testicular Toxicity in Male Rats

Molecules ◽

10.3390/molecules26020408 ◽

2021 ◽

Vol 26 (2) ◽

pp. 408

Author(s):

Sherif R. Abdel-All ◽

Zeinab T. Abdel Shakour ◽

Dalia M. N. Abouhussein ◽

Enji Reda ◽

Thoraya F. Sallam ◽

...

Keyword(s):

Antineoplastic Agent ◽

Biological Evaluation ◽

Particle Size Analysis ◽

Male Rats ◽

Size Analysis ◽

Dilution Method ◽

Tribulus Terrestris ◽

Testicular Toxicity ◽

Transmission Electron ◽

Male Wistar Rats

The incorporation of cisplatin (CP) as a cytotoxic antineoplastic agent in most chemotherapeutic protocols is a challenge due to its toxic effect on testicular tissues. Natural compounds present a promising trend in research, so a new nutraceutical formulation (NCF) was designed to diminish CP spermatotoxicity. A combination of three nutraceutical materials, 250 mg Spirulina platensis powder (SP), 25 mg Tribulus terrestris L. extract (TT), and 100 mg fish oil (FO) were formulated in self-nanoemulsifying self-nanosuspension (SNESNS). SP was loaded into the optimized self-nanoemulsifying system (30% FO, 50% span 80/cremophor EL and 20% isopropanol) and mixed with TT aqueous solution to form SNESNS. For the SP, phytochemical profiling revealed the presence of valuable amounts of fatty acids (FAs), amino acids, flavonoids, polyphenols, vitamins, and minerals. Transmission electron microscopy (TEM) and particle size analysis confirmed the formation of nanoemulsion-based nanosuspension upon dilution. Method validation of the phytochemical constituents in NCF has been developed. Furthermore, NCF was biologically evaluated on male Wistar rats and revealed the improvement of spermatozoa, histopathological features, and biochemical markers over the CP and each ingredient group. Our findings suggest the potential of NCF with SNESNS as a delivery system against CP-induced testicular toxicity in male rats.

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Synthesis and Characterization of Folate-Modified Cell Membrane Mimetic Copolymer Micelles for Effective Tumor Cell Internalization

ACS Applied Bio Materials ◽

10.1021/acsabm.0c01612 ◽

2021 ◽

Author(s):

Wei Du ◽

Qian Lu ◽

Mengchen Zhang ◽

Haimei Cao ◽

Shiping Zhang

Keyword(s):

Cell Membrane ◽

Tumor Cell ◽

Synthesis And Characterization ◽

Cell Internalization ◽

Membrane Mimetic ◽

Copolymer Micelles

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Hybrid-Type SELEX for the Selection of Artificial Nucleic Acid Aptamers Exhibiting Cell Internalization Activity

Pharmaceutics ◽

10.3390/pharmaceutics13060888 ◽

2021 ◽

Vol 13 (6) ◽

pp. 888

Author(s):

Hiro Uemachi ◽

Yuuya Kasahara ◽

Keisuke Tanaka ◽

Takumi Okuda ◽

Yoshihiro Yoneda ◽

...

Keyword(s):

Nucleic Acid ◽

Surface Protein ◽

Functional Screening ◽

Nucleic Acid Aptamers ◽

Hybrid Type ◽

Cell Internalization ◽

Promising Target ◽

A Cell ◽

Exponential Enrichment

Nucleic acid aptamers have attracted considerable attention as next-generation pharmaceutical agents and delivery vehicles for small molecule drugs and therapeutic oligonucleotides. Chemical modification is an effective approach for improving the functionality of aptamers. However, the process of selecting appropriately modified aptamers is laborious because of many possible modification patterns. Here, we describe a hybrid-type systematic evolution of ligands by exponential enrichment (SELEX) approach for the generation of the artificial nucleic acid aptamers effective against human TROP2, a cell surface protein identified by drug discovery as a promising target for cancer therapy. Capillary electrophoresis SELEX was used for the pre-screening of multiple modified nucleic acid libraries and enrichment of TROP2 binding aptamers in the first step, followed by functional screening using cell-SELEX in the second step for the generation of cell-internalizing aptamers. One representative aptamer, Tac-B1, had a nanomolar-level affinity to human TROP2 and exhibited elevated capacity for internalization by cells. Because of the growing interest in the application of aptamers for drug delivery, our hybrid selection approach has great potential for the generation of functional artificial nucleic acid aptamers with ideal modification patterns in vitro.

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