LHH1, a novel antimicrobial peptide with anti-cancer cell activity identified from Lactobacillus casei HZ1

Abstract Antimicrobial peptides have been attracting increasing attention for their multiple beneficial effects. In present study, a novel AMP with a molecular weight of 1875.5 Da, was identified from the genome of Lactobacillus casei HZ1. The peptide, which was named as LHH1 was comprised of 16 amino acid residues, and its α-helix content was 95.34% when dissolved in 30 mM SDS. LHH1 exhibited a broad range of antimicrobial activities against Gram-positive bacteria and fungus. It could effectively inhibit Staphylococcus aureus with a minimum inhibitory concentration of 3.5 μM and showed a low hemolytic activity. The scanning electron microscope, confocal laser scanning microscope and flow cytometry results showed that LHH1 exerted its antibacterial activity by damaging the cell membrane of Staphylococcus aureus. Meanwhile, LHH1 also exhibited anti-cancer cell activities against several cancer cells via breaking the cell membrane of MGC803, HCT116 and C666-1 cancer cells.

Download Full-text

LHH1, a Novel Antimicrobial Peptide with Anti-Cancer Cell Activity Identified from Lactobacillus casei HZ1

10.21203/rs.3.rs-44740/v2 ◽

2020 ◽

Author(s):

Junfang He ◽

Duxin Jin ◽

Xuegang Luo ◽

Tongcun Zhang

Keyword(s):

Staphylococcus Aureus ◽

Cell Membrane ◽

Cancer Cells ◽

Cancer Cell ◽

Lactobacillus Casei ◽

Laser Scanning ◽

Cell Activity ◽

Antimicrobial Activities ◽

Confocal Laser ◽

Anti Cancer

Download Full-text

LHH1, a Novel Antimicrobial Peptide with Anti-Cancer Activity Identified from Lactobacillus casei HZ1

10.21203/rs.3.rs-44740/v1 ◽

2020 ◽

Author(s):

Junfang He ◽

Duxin Jin ◽

Xuegang Luo ◽

Tongcun Zhang

Keyword(s):

Staphylococcus Aureus ◽

Cell Membrane ◽

Lactobacillus Casei ◽

Laser Scanning ◽

Antimicrobial Activities ◽

Confocal Laser Scanning Microscope ◽

Confocal Laser ◽

Beneficial Effects ◽

Anti Cancer ◽

Α Helix

Abstract Antimicrobial peptides have been attracting increasing attention for their multiple beneficial effects. In present study, a novel AMP with a molecular weight of 1875.25 Da, was identified from the genome of Lactobacillus casei HZ1. The peptide, which was named as LHH1 was comprised of 16 amino acid residues, and its α-helix content was 95.34% when dissolved in 30 mM SDS. LHH1 exhibited a broad range of antimicrobial activities against gram-positive bacteria and fungus. It could effectively inhibit staphylococcus aureus with a minimum inhibitory concentration of 3.5 μM and showed a low hemolytic activity. The scanning electron microscope, confocal laser scanning microscope and flow cytometry results showed that LHH1 exerted its antibacterial activity by damaging the cell membrane of staphylococcus aureus. Meanwhile, LHH1 also exhibited anti-cancer activities against several cancer cells including MGC803, HCT116 and C666-1 cells, and one major action of its anti-cancer mechanism was breaking the cell membrane.

Download Full-text

Oxidation-Triggerable Liposome Incorporating Poly(Hydroxyethyl Acrylate-co-Allyl methyl sulfide) as an Anticancer Carrier of Doxorubicin

Cancers ◽

10.3390/cancers12010180 ◽

2020 ◽

Vol 12 (1) ◽

pp. 180 ◽

Cited By ~ 3

Author(s):

Jin Ah Kim ◽

Dong Youl Yoon ◽

Jin-Chul Kim

Keyword(s):

Cancer Cells ◽

Surface Activity ◽

Laser Scanning ◽

Drug Carriers ◽

Laser Scanning Microscopy ◽

Cancer Drug ◽

Confocal Laser ◽

H2o2 Treatment ◽

Methyl Sulfide ◽

Anti Cancer

Since cancer cells are oxidative in nature, anti-cancer agents can be delivered to cancer cells specifically without causing severe normal cell toxicity if the drug carriers are designed to be sensitive to the intrinsic characteristic. Oxidation-sensitive liposomes were developed by stabilizing dioleoylphosphatidyl ethanolamine (DOPE) bilayers with folate-conjugated poly(hydroxyethyl acrylate-co-allyl methyl sulfide) (F-P(HEA-AMS)). The copolymer, synthesized by a free radical polymerization, was surface-active but lost its surface activity after AMS unit was oxidized by H2O2 treatment. The liposomes with F-P(HEA-AMS) were sensitive to H2O2 concentration (0%, 0.5%, 1.0%, and 2.0%) in terms of release, possibly because the copolymer lost its surface activity and its bilayer-stabilizing ability upon oxidation. Fluorescence-activated cell sorting (FACS) and confocal laser scanning microscopy (CLSM) revealed that doxorubicin (DOX)-loaded liposomes stabilized with folate-conjugated copolymers markedly promoted the transport of the anti-cancer drug to cancer cells. This was possible because the liposomes were readily translocated into the cancer cells via receptor-mediated endocytosis. This liposome would be applicable to the delivery carrier of anticancer drugs.

Download Full-text

Aptamer-Aptamer Chimera for Targeted Delivery and ATP-Responsive Release of Doxorubicin into Cancer Cells

International Journal of Molecular Sciences ◽

10.3390/ijms222312940 ◽

2021 ◽

Vol 22 (23) ◽

pp. 12940

Author(s):

Ezaldeen Esawi ◽

Walhan Alshaer ◽

Ismail Sami Mahmoud ◽

Dana A. Alqudah ◽

Bilal Azab ◽

...

Keyword(s):

Cancer Cells ◽

Cancer Cell ◽

Targeted Delivery ◽

Laser Scanning ◽

Laser Scanning Microscopy ◽

Confocal Laser ◽

Innovative Drug ◽

Great Opportunity ◽

Selective Delivery ◽

In Cells

Aptamers offer a great opportunity to develop innovative drug delivery systems that can deliver cargos specifically into targeted cells. In this study, a chimera consisting of two aptamers was developed to deliver doxorubicin into cancer cells and release the drug in cytoplasm in response to adenosine-5′-triphosphate (ATP) binding. The chimera was composed of the AS1411 anti-nucleolin aptamer for cancer cell targeting and the ATP aptamer for loading and triggering the release of doxorubicin in cells. The chimera was first produced by hybridizing the ATP aptamer with its complementary DNA sequence, which is linked with the AS1411 aptamer via a poly-thymine linker. Doxorubicin was then loaded inside the hybridized DNA region of the chimera. Our results show that the AS1411–ATP aptamer chimera was able to release loaded doxorubicin in cells in response to ATP. In addition, selective uptake of the chimera into cancer cells was demonstrated using flow cytometry. Furthermore, confocal laser scanning microscopy showed the successful delivery of the doxorubicin loaded in chimeras to the nuclei of targeted cells. Moreover, the doxorubicin-loaded chimeras effectively inhibited the growth of cancer cell lines and reduced the cytotoxic effect on the normal cells. Overall, the results of this study show that the AS1411–ATP aptamer chimera could be used as an innovative approach for the selective delivery of doxorubicin to cancer cells, which may improve the therapeutic potency and decrease the off-target cytotoxicity of doxorubicin.

Download Full-text

Efficacy of Chelerythrine Against Mono- and Dual-Species Biofilms of Candida albicans and Staphylococcus aureus and Its Properties of Inducing Hypha-to-Yeast Transition of C. albicans

Journal of Fungi ◽

10.3390/jof6020045 ◽

2020 ◽

Vol 6 (2) ◽

pp. 45 ◽

Cited By ~ 2

Author(s):

Weidong Qian ◽

Jianing Zhang ◽

Wenjing Wang ◽

Miao Liu ◽

Yuting Fu ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Candida Albicans ◽

Laser Scanning ◽

Fluorescent Dyes ◽

Hyphal Growth ◽

Antimicrobial Activities ◽

Confocal Laser Scanning Microscope ◽

Confocal Laser ◽

Life Threatening ◽

And Staphylococcus Aureus

Candida albicans and Staphylococcus aureus specifically often resulted in biofilm-associated diseases, ranging from superficial mucosal to life-threatening systemic infections. Recent studies reported that chelerythrine displayed antimicrobial activities against a few microorganisms, but its effects on mono- and dual-species biofilms of C. albicans and S. aureus have never been reported. The purpose of this study was to evaluate the efficacy of chelerythrine against mono- and dual-species biofilms, and explore its effect on the hyphal growth and the hypha-to-yeast transition of C. albicans. The results showed that minimum inhibitory concentrations (MICs) and minimum biofilm inhibitory concentration (MBIC90S) of chelerythrine against planktonic cells of mono-species were 4 and 2 μg/mL, while the MIC and MBIC90 were 6 and 3 μg/mL for dual-species. Meanwhile, the decrease in three matrix component levels and tolerance to antibiotics of biofilms formed by mono- and dual-species exposed to chelerythrine were confirmed by a confocal laser scanning microscope, in conjugation with five fluorescent dyes and a gatifloxacin diffusion assay. Moreover, C. albicans and S. aureus mono-species showed a 96.4, and 92.3% reduction, respectively, in 24-h preformed biofilm biomass in the presence of 128 µg/mL of chelerythrine. Similarly, preformed (24 h) dual-species biofilm biomass also displayed a significant reduction (90.7%) when treated with 192 μg/mL chelerythrine. Chelerythrine inhibited hyphae formation of C. albicans at 4 μg/mL, and C. albicans in hypha-form can be converted into yeast-form at 8 μg/mL of chelerythrine. Therefore, chelerythrine shows promise as a potential antimicrobial and antibiofilm agent for clinical effective treatments of mono- and mixed-species and/or biofilm-associated infections.

Download Full-text

Theoretical Study of the Process of Passage of Glycoside Amides through the Cell Membrane of Cancer Cell

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620999201103201008 ◽

2020 ◽

Vol 20 ◽

Author(s):

Vasil Tsanov ◽

Hristo Tsanov

Keyword(s):

Cell Membrane ◽

Cancer Cells ◽

Cancer Cell ◽

Quantum Chemical ◽

Density Functional ◽

Enzyme Regulation ◽

Amide Derivatives ◽

Pass Through ◽

Hydrolysis Of ◽

Derivatives Of

Background:: This article concentrates on the processes occurring in the medium around the cancer cell and the transfer of glycoside amides through their cell membrane. They are obtained by modification of natural glycoside-nitriles (cyano-glycosides). Hydrolysis of starting materials in the blood medium and associated volume around physiologically active healthy and cancer cells, based on quantum-chemical semi-empirical methods, is considered. Objective:: Based on the fact that the cancer cell feeds primarily on carbohydrates, it is likely that organisms have adapted to take food containing nitrile glycosides and / or modified forms to counteract "external" bioactive activity. Cancers, for their part, have evolved to create conditions around their cells that eliminate their active apoptotic forms. This is far more appropriate for them than changing their entire enzyme regulation to counteract it. In this way, it protects itself and the gene sets and develops according to its instructions. Methods:: Derived pedestal that closely defines the processes of hydrolysis in the blood, the transfer of a specific molecular hydrolytic form to the cancer cell membrane and with the help of time-dependent density-functional quantum- chemical methods, its passage and the processes of re-hydrolysis within the cell itself, to forms causing chemical apoptosis of the cell - independent of its non-genetic set, which seeks to counteract the process. Results:: Used in oncology it could turn a cancer from a lethal to a chronic disease (such as diabetes). The causative agent and conditions for the development of the disease are not eliminated, but the amount of cancer cells could be kept low for a long time (even a lifetime). Conclusion:: The amide derivatives of nitrile glycosides exhibit anti-cancer activity, the cancer cell probably seeks to displace hydrolysis of these derivatives in a direction that would not pass through its cell membrane and the amide- carboxyl derivatives of nitrile glycosides could deliver extremely toxic compounds within the cancer cell itself and thus block and / or permanently damage its normal physiology.

Download Full-text

Adenosine Analogues as Opposite Modulators of the Cisplatin Resistance of Ovarian Cancer Cells

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520619666190118113201 ◽

2019 ◽

Vol 19 (4) ◽

pp. 473-486 ◽

Cited By ~ 1

Author(s):

Katarzyna Bednarska-Szczepaniak ◽

Damian Krzyżanowski ◽

Magdalena Klink ◽

Marek Nowak

Keyword(s):

Cell Cycle ◽

Ovarian Cancer ◽

Cancer Cells ◽

Cancer Cell ◽

Cell Biology ◽

Immune Cell ◽

Immunosuppressive Agents ◽

Cell Activity ◽

Ovarian Cancer Cells ◽

Adenosine Analogues

Background: Adenosine released by cancer cells in high amounts in the tumour microenvironment is one of the main immunosuppressive agents responsible for the escape of cancer cells from immunological control. Blocking adenosine receptors with adenosine analogues and restoring immune cell activity is one of the methods considered to increase the effectiveness of anticancer therapy. However, their direct effects on cancer cell biology remain unclear. Here, we determined the effect of adenosine analogues on the response of cisplatinsensitive and cisplatin-resistant ovarian cancer cells to cisplatin treatment. Methods: The effects of PSB 36, DPCPX, SCH58261, ZM 241385, PSB603 and PSB 36 on cisplatin cytotoxicity were determined against A2780 and A2780cis cell lines. Quantification of the synergism/ antagonism of the compounds cytotoxicity was performed and their effects on the cell cycle, apoptosis/necrosis events and cisplatin incorporation in cancer cells were determined. Results: PSB 36, an A1 receptor antagonist, sensitized cisplatin-resistant ovarian cancer cells to cisplatin from low to high micromolar concentrations. In contrast to PSB 36, the A2AR antagonist ZM 241385 had the opposite effect and reduced the influence of cisplatin on cancer cells, increasing their resistance to cisplatin cytotoxicity, decreasing cisplatin uptake, inhibiting cisplatin-induced cell cycle arrest, and partly restoring mitochondrial and plasma membrane potentials that were disturbed by cisplatin. Conclusion: Adenosine analogues can modulate considerable sensitivity to cisplatin of ovarian cancer cells resistant to cisplatin. The possible direct beneficial or adverse effects of adenosine analogues on cancer cell biology should be considered in the context of supportive chemotherapy for ovarian cancer.

Download Full-text

Prediction and Activity of a Cationic α-Helix Antimicrobial Peptide ZM-804 from Maize

International Journal of Molecular Sciences ◽

10.3390/ijms22052643 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2643

Author(s):

Mohamed F. Hassan ◽

Abdelrahman M. Qutb ◽

Wubei Dong

Keyword(s):

Cdna Library ◽

Pseudomonas Syringae ◽

Inbred Line ◽

Mammalian Cells ◽

Laser Scanning ◽

Pathogenic Bacteria ◽

Antimicrobial Activities ◽

Confocal Laser ◽

In Planta ◽

Minimal Inhibitory Concentrations

Antimicrobial peptides (AMPs) are small molecules consisting of less than fifty residues of amino acids. Plant AMPs establish the first barrier of defense in the innate immune system in response to invading pathogens. The purpose of this study was to isolate new AMPs from the Zea mays L. inbred line B73 and investigate their antimicrobial activities and mechanisms against certain essential plant pathogenic bacteria. In silico, the Collection of Anti-Microbial Peptides (CAMPR3), a computational AMP prediction server, was used to screen a cDNA library for AMPs. A ZM-804 peptide, isolated from the Z. mays L. inbred line B73 cDNA library, was predicted as a new cationic AMP with high prediction values. ZM-804 was tested against eleven pathogens of Gram-negative and Gram-positive bacteria and exhibited high antimicrobial activities as determined by the minimal inhibitory concentrations (MICs) and the minimum bactericidal concentrations (MBCs). A confocal laser scanning microscope observation showed that the ZM-804 AMP targets bacterial cell membranes. SEM and TEM images revealed the disruption and damage of the cell membrane morphology of Clavibacter michiganensis subsp. michiganensis and Pseudomonas syringae pv. tomato (Pst) DC3000 caused by ZM-804. In planta, ZM-804 demonstrated antimicrobial activity and prevented the infection of tomato plants by Pst DC3000. Moreover, four virulent phytopathogenic bacteria were prevented from inducing hypersensitive response (HR) in tobacco leaves in response to low ZM-804 concentrations. ZM-804 exhibits low hemolytic activity against mouse red blood cells (RBCs) and is relatively safe for mammalian cells. In conclusion, the ZM-804 peptide has a strong antibacterial activity and provides an alternative tool for plant disease control. Additionally, the ZM-804 peptide is considered a promising candidate for human and animal drug development.

Download Full-text

Quantum Dots as a Good Carriers of Unsymmetrical Bisacridines for Modulating Cellular Uptake and the Biological Response in Lung and Colon Cancer Cells

Nanomaterials ◽

10.3390/nano11020462 ◽

2021 ◽

Vol 11 (2) ◽

pp. 462 ◽

Cited By ~ 1

Author(s):

Joanna Pilch ◽

Patrycja Kowalik ◽

Piotr Bujak ◽

Anna M. Nowicka ◽

Ewa Augustin

Keyword(s):

Quantum Dots ◽

Cancer Cells ◽

Cellular Uptake ◽

Laser Scanning ◽

Biological Response ◽

Drug Carriers ◽

Confocal Laser ◽

Normal Cells ◽

H460 Cells ◽

Hct116 Cells

Nanotechnology-based drug delivery provides a promising area for improving the efficacy of cancer treatments. Therefore, we investigate the potential of using quantum dots (QDs) as drug carriers for antitumor unsymmetrical bisacridine derivatives (UAs) to cancer cells. We examine the influence of QD–UA hybrids on the cellular uptake, internalization (Confocal Laser Scanning Microscope), and the biological response (flow cytometry and light microscopy) in lung H460 and colon HCT116 cancer cells. We show the time-dependent cellular uptake of QD–UA hybrids, which were more efficiently retained inside the cells compared to UAs alone, especially in H460 cells, which could be due to multiple endocytosis pathways. In contrast, in HCT116 cells, the hybrids were taken up only by one endocytosis mechanism. Both UAs and their hybrids induced apoptosis in H460 and HCT116 cells (to a greater extent in H460). Cells which did not die underwent senescence more efficiently following QDs–UAs treatment, compared to UAs alone. Cellular senescence was not observed in HCT116 cells following treatment with both UAs and their hybrids. Importantly, QDgreen/red themselves did not provoke toxic responses in cancer or normal cells. In conclusion, QDs are good candidates for targeted UA delivery carriers to cancer cells while protecting normal cells from toxic drug activities.

Download Full-text