Melatonin and cancer: From the promotion of genomic stability to use in cancer treatment

Cancer remains among the most challenging human diseases. Several lines of evidence suggest that carcinogenesis is a complex process that is initiated by DNA damage. Exposure to clastogenic agents such as heavy metals, ionizing radiation (IR), and chemotherapy drugs may cause chronic mutations in the genomic material, leading to a phenomenon named genomic instability. Evidence suggests that genomic instability is responsible for cancer incidence after exposure to carcinogenic agents, and increases the risk of secondary cancers following treatment with radiotherapy or chemotherapy. Melatonin as the main product of the pineal gland is a promising hormone for preventing cancer and improving cancer treatment. Melatonin can directly neutralize toxic free radicals more efficiently compared with other classical antioxidants. In addition, melatonin is able to regulate the reduction/oxidation (redox) system in stress conditions. Through regulation of mitochondrial nction and inhibition of pro-oxidant enzymes, melatonin suppresses chronic oxidative stress. Moreover, melatonin potently stimulates DNA damage responses that increase the tolerance of normal tissues to toxic effect of IR and may reduce the risk of genomic instability in patients who undergo radiotherapy. Through these mechanisms, melatonin attenuates several side effects of radiotherapy and chemotherapy. Interestingly, melatonin has shown some synergistic properties with IR and chemotherapy, which is distinct from classical antioxidants that are mainly used for the alleviation of adverse events of radiotherapy and chemotherapy. In this review, we describe the anticarcinogenic effects of melatonin and also its possible application in clinical oncology.     

In vitro cytotoxicity and DNA/HSA interaction study of triamterene using molecular modelling and multi-spectroscopic methods

The anticancer activity of triamterene on HCT116 and CT26 colon cancer cells lines was investigated. Furthermore, the mechanism of interaction between triamterene and calf thymus DNA (ct-DNA) and also human serum albumin (HSA) was conducted using spectroscopic and molecular docking techniques. In vitro cytotoxicity of triamterene against HCT116 and CT26 cells showed promising anticancer effects with IC50 values of 31.30 and 24.45 μM, respectively. Competitive studies of the triamterene with NR (neutral red) and MB (methylene blue) as intercalator probes showed that triamterene can be replaced by these probes. The viscosity data also confirmed that triamterene binds to calf–thymus DNA through intercalation binding mode. Binding properties of triamterene with HSA in the presence of warfarin and ibuprofen showed that triamterene competes with warfarin for the site I of human serum albumin (HSA). In addition, the binding modes of triamterene with DNA and HSA were verified by molecular docking technique. Abbreviations ct-DNA calf thymus DNA

CV cyclic voltammetry

DNA deoxyribonucleic acid

DPV differential pulse voltammetry

FBS fetal bovine serum

HSA human serum albumin

NR neutral red

MB methylene blue

MTT 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazoliumbromide

Communicated by Ramaswamy H. Sarma     

The Role of Storage Lipids in the Relation between Fecundity,Locomotor Activity,and Lifespan of Drosophila melanogaster Longevity-Selected and Control Lines

The contribution of insect fat body to multiple processes, such as development, metamorphosis, activity, and reproduction results in trade-offs between life history traits. In the present study, age-induced modulation of storage lipid composition in Drosophila melanogaster longevity-selected (L) and non-selected control (C) lines was studied and the correlation between total body fat mass and lifespan assessed. The trade-offs between fecundity, locomotor activity, and lifespan were re-evaluated from a lipid-related metabolic perspective. Fewer storage lipids in the L lines compared to the C lines supports the impact of body fat mass on extended lifespan. The higher rate of fecundity and locomotor activity in the L lines may increase the lipid metabolism and enhance the lipolysis of storage lipids, reducing fat reserves. The correlation between neutral lipid fatty acids and fecundity, as well as locomotor activity, varied across age groups and between the L and C lines. The fatty acids that correlated with egg production were different from the fatty acids that correlated with locomotor activity. The present study suggests that fecundity and locomotor activity may positively affect the lifespan of D. melanogaster through the inhibition of fat accumulation.     

Supercritical CO2 Generation of Nanometric Structure from Ocimum basilicum Mucilage Prepared for Pharmaceutical Applications

Plant-derived polymers are widely used in the pharmaceutical industry due to their emollient, lack of toxicity, and irritating nature and low cost. In this work, basil seed mucilage was dried using supercritical carbon dioxide phase inversion technique to form a nanometric structure. The obtained polymeric structures were characterized by scanning electron microscopy (SEM), Brunauer–Emmett–Teller (BET) method, and Fourier transform infrared spectroscopy (FTIR) and compared with the oven-derived sample group. It was demonstrated that the product morphology could be controlled by altering the composition of methanol which functioned as the co-solvent in the nonsolvent stream. The most homogeneous product (60-nm mean pore size diameter, 78 m²/g BET surface area with no agglomeration) was obtained with 2.5% methanol. The FTIR data showed that the presence of hydroxyl and carboxyl groups suggested the bioadhesive property of basil seed mucilage was good and many active pharmaceutical compounds might be loaded to the resultant nanometric structure to enhance drug release. Furthermore, the FTIR analyses indicated that the nature of the final product did not change during the supercritical drying procedure.KEY WORDS: basil seed gum, drug delivery, FTIR characterization, nanostructure, natural polymer, supercritical phase inversion     

Electrospinning of Cross-Linked Magnetic Chitosan Nanofibers for Protein Release

A poly(vinylalcohol) (PVA) electrospun/magnetic/chitosan nanocomposite fibrous cross-linked network was fabricated using in situ cross-linking electrospinning technique and used for bovine serum albumin (BSA) loading and release applications. Sodium tripolyphosphate (TPP) and glutaraldehyde (GA) were used as cross-linkers which modified magnetic-Fe₃O₄ chitosan as Fe₃O_4/CS/TPP and Fe₃O_4/CS/GA, respectively. BSA was used as a model protein drugs which was encapsulated to form Fe₃O₄/CS/TPP/BSA and Fe₃O₄/CS/GA/BSA nanoparticles. The composites were electrospun with PVA to form nanofibers. Nanofibers were characterized by field emission scanning electron microscopy (FESEM) and Fourier transform infrared spectroscopy (FTIR). The characterization results suggest that Fe₃O₄ nanoparticles with average size of 45 nm were successfully bound on the surface of chitosan. The cross-linked nanofibers were found to contain uniformly dispersed Fe₃O₄ nanoparticles. The size and morphology of the nanofibers network was controlled by varying the cross-linker type. FTIR data show that these two polymers have intermolecular interactions. The sample with TPP cross-linker showed an enhancement of the controlled release properties of BSA during 30-h experimental investigation.

Graphical Abstract

Open in a separate windowᅟKEY WORDS: cross-linker, electrospun, magnetite, mano-composite, protein loading     

Application of nanoparticles in cancer therapy with an emphasis on cell cycle

Owing to their unique characteristics, nanoparticles (NPs) could be incorporated into valuable therapeutic modalities for different diseases; however, there are many concerns about risk factors in human applications. NPs carry therapeutic chemicals that could improve the outcome of cancer therapies. Nowadays, NPs are being recognized as important and strategic agents in treatment of several disorders due to their unique properties in targeting malignant cells in tumor sites. Numerous investigations have shown that the majority of chemotherapeutic agents can be modified through entrapment in submicron colloidal systems. Still, there are problems and limitations in application of NPs in cancer therapy. The aim of the present study is to focus on potential NPs usage in cancer treatment with an emphasis on the cell cycle of malignant cells.     

Comparison of Cytokine Expression in Human PBMCs Stimulated with Normal and Heat-Shocked Lactobacillus plantarum Cell Lysate

Probiotics and Antimicrobial Proteins - Regulation of immune responses is among the beneficial effects of probiotic bacteria on human health. In this study, we aim to investigate the effect of...     

Misdiagnosis and exacerbation of unusual obsessive-compulsive disorder presentation with risperidone and clozapine in an adolescent girl - A case report

Obsessive-compulsive disorder (OCD) is a heterogenous disorder with different clinical presentations. The most common symptoms are those that involve contamination, possible harm, ordering/symmetry, aggressive/sexual/religious concerns and hoarding. A variety of less common symptoms have been described. Unusual OCD symptoms may lead to misdiagnosis, inappropriate treatment with possible serious side effects. In this report we present a case of an adolescent girl in which unusual OCD presentation and symptoms were misinterpreted to represent psychosis and exacerbation of OCD symptoms with risperidone and clozapine treatment. We discuss the possible pathophysiological mechanisms of OCD symptom exacerbation, clinical implications, and successful management of this case, with fluvoxamine therapy. This case may represent the first report of musical obsessions successfully managed with fluvoxamine therapy.