The Zinc-Schiff Base-Novicidin Complex as a Potential Prostate Cancer Therapy

Milosavljević, Vedran; Haddad, Yazan; Rodrigo, Miguel Ángel Merlos; Moulick, Amitava; Polanská, Hana; Hynek, David; Heger, Zbyněk; Kopel, Pavel; Adam, Vojtěch

doi:10.1371/journal.pone.0163983

Cited by 23 publications

(24 citation statements)

References 67 publications

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“…Furthermore, multiple studies have revealed that SLC30A family genes are dysregulated and played a critical role in various kinds of cancer, including pancreatic cancer 18 , invasive breast ductal carcinoma 18 , and esophageal cell carcinoma 20 . Previous studies have reported that SLC30A1 , 9 and 10 were significantly upregulated in prostate cancer tissues compared to normal tissues, while SLC30A5 - 6 were strongly downregulated 21 – 23 . Upregulated SLC30A5-7 expression might play a critical role in coordinating transcriptional programming associated with the increased activity of the early secretory pathway in colorectal cancer 24 .…”

Section: Introductionmentioning

confidence: 86%

Comprehensive analysis of the expression of SLC30A family genes and prognosis in human gastric cancer

Guo

2020

Sci Rep

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The solute carrier 30 (SLC30) family genes play a fundamental role in various cancers. However, the diverse expression patterns, prognostic value, and potential mechanism of SLC30A family genes in gastric cancer (GC) remain unknown. Herein, we analyzed the expression and survival data of SLC30A family genes in GC patients using multiple bioinformatic approaches. Expression data of SLC30A family genes for GC patients were extracted from the Cancer Genome Atlas (TCGA) and genetic alteration frequency assessed by using cBioportal database. And validated the expression of SLC30A family genes in GC tissues and corresponding normal tissues. The prognostic value of SLC30A family genes in gastric cancer patients were explored using Kaplan–Meier plotter database. Functional enrichment analysis performed using DAVID database and clusterProfiler package. And ssGSEA algorithm was performed to explore the relationship between the SLC30A family genes and the infiltration of immune cells. We found that the median expression levels of SLC30A1-3, 5–7, and 9 were significantly upregulated in gastric cancer tissues compared to non-cancerous tissues, while SLC30A4 was downregulated. Meanwhile, SLC30A1-7, and 9 were significantly correlated with advanced tumor stage and nodal metastasis status, SLC30A5-7, and 9–10 were significantly related to the Helicobacter pylori infection status of GC patients. High expression of five genes (SLC30A1, 5–7, and 9) was significantly correlated with better overall survival (OS), first progression survival (FPS), and post progression survival (PPS). Conversely, upregulated SLC30A2-4, 8, and 10 expression was markedly associated with poor OS, FP and PPS. And SLC30A family genes were closely associated with the infiltration of immune cells. The present study implied that SLC30A5 and 7 may be potential biomarkers for predicting prognosis in GC patients, SLC30A2 and 3 play an oncogenic role in GC patients and could provide a new strategy for GC patients treatment.

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Section: Introductionmentioning

confidence: 86%

Comprehensive analysis of the expression of SLC30A family genes and prognosis in human gastric cancer

Guo

2020

Sci Rep

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“…The optical bright field microscopic ( Boulos et al, 1999 ) image analysis was also performed for both peptides with respective MIC values of PBDM peptides against S. aureus , MRSA, VRSA, E. faecalis , VRE, and E. coli , with number of cells visualized per samples was observed from 10 randomized microscopic grid fields. Furthermore, VRSA samples were incubated with PBDM peptide conjugates for 4 h at 37°C in a shaking incubator and observed under microscope ( Milosavljevic et al, 2016 ; Hussain et al, 2018 ; Mazumdar et al, 2020 ). The number of cells visualized per samples was observed from 10 randomized microscopic grid fields.…”

Section: Methodsmentioning

confidence: 99%

Characterization and in vitro Analysis of Probiotic-Derived Peptides Against Multi Drug Resistance Bacterial Infections

et al. 2020

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An inexorable switch from antibiotics has become a major desideratum to overcome antibiotic resistance. Bacteriocin from Lactobacillus casei , a cardinal probiotic was used to design novel antibacterial peptides named as Probiotic Bacteriocin Derived and Modified (PBDM) peptides (PBDM1: YKWFAHLIKGLC and PBDM2: YKWFRHLIKKLC). The loop-shaped 3D structure of peptides was characterized in silico via molecular dynamics simulation as well as biophysically via spectroscopic methods. Thereafter, in vitro results against multidrug resistant bacterial strains and hospital samples demonstrated the strong antimicrobial activity of PBDM peptides. Further, in vivo studies with PBDM peptides showed downright recovery of balb/c mice from Vancomycin Resistant Staphylococcus aureus (VRSA) infection to its healthy condition. Thereafter, in vitro study with human epithelial cells showed no significant cytotoxic effects with high biocompatibility and good hemocompatibility. In conclusion, PBDM peptides displayed significant antibacterial activity against certain drug resistant bacteria which cause infections in human beings. Future analysis are required to unveil its mechanism of action in order to execute it as an alternative to antibiotics.

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“…Adam and co-workers [ 210 ] proposed the use of the membrane-penetrating peptide Novicidin (NVC) [ 211 ] conjugated with the Schiff base-zinc complex 39 ( Figure 20 ) as a carrier vehicle for the delivery of zinc to human prostate cancer cells. Molecular analyses were used to confirm the activation of zinc stress (e.g., ZnT-1) and apoptosis (e.g., CASP-1) genes.…”

Section: Schiff Base Systemsmentioning

confidence: 99%

“…NVC alone reduced cell viability by 50% at a concentration of 16 nM and by 100% at 63 nM after 24, in both PC3 and PNT1A cell lines. The 39 complex without peptide also displayed meaningful toxicity toward both cell lines compared with NVC alone, reducing cell viability by 40% at 125 nM and by 100% at 250 nM after 24 h. 39 -NVC complex reduced cell viability in PC3 cell line by 65% at a concentration of 46 nM, but in PNT1A cells it showed negligible cytotoxicity, even at a concentration of 500 nM [ 210 ]. Zinc uptake was confirmed in both cell lines.…”

Section: Schiff Base Systemsmentioning

confidence: 99%

Zinc Complexes with Nitrogen Donor Ligands as Anticancer Agents

et al. 2020

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The search for anticancer metal-based drugs alternative to platinum derivatives could not exclude zinc derivatives due to the importance of this metal for the correct functioning of the human body. Zinc, the second most abundant trace element in the human body, is one of the most important micro-elements essential for human physiology. Its ubiquity in thousands of proteins and enzymes is related to its chemical features, in particular its lack of redox activity and its ability to support different coordination geometries and to promote fast ligands exchange. Analogously to other trace elements, the impairment of its homeostasis can lead to various diseases and in some cases can be also related to cancer development. However, in addition to its physiological role, zinc can have beneficial therapeutic and preventive effects on infectious diseases and, compared to other metal-based drugs, Zn(II) complexes generally exert lower toxicity and offer few side effects. Zinc derivatives have been proposed as antitumor agents and, among the great number of zinc coordination complexes which have been described so far, this review focuses on the design, synthesis and biological studies of zinc complexes comprising N-donor ligands and that have been reported within the last five years.

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The Zinc-Schiff Base-Novicidin Complex as a Potential Prostate Cancer Therapy

Cited by 23 publications

References 67 publications

Comprehensive analysis of the expression of SLC30A family genes and prognosis in human gastric cancer

Comprehensive analysis of the expression of SLC30A family genes and prognosis in human gastric cancer

Characterization and in vitro Analysis of Probiotic-Derived Peptides Against Multi Drug Resistance Bacterial Infections

Zinc Complexes with Nitrogen Donor Ligands as Anticancer Agents

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