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Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 409
Author(s):  
Alicja Chrzanowska ◽  
Wioletta Olejarz ◽  
Grażyna Kubiak-Tomaszewska ◽  
Andrzej K. Ciechanowicz ◽  
Marta Struga

Purpose: To assess cytotoxic effect of ciprofloxacin conjugates with fatty acids on prostate cancer cells (LNCaP and DU-145) with different hormone sensitivity, based on previous promising results from the PC3 cells. Methods: Cytotoxicity were estimated using MTT and LDH tests, whereas its mechanisms were estimated by apoptosis and IL-6 assays. The intensity of proteins involved in lipid metabolism was determined using ML-CS assay. Results: The hormone insensitive DU-145 cells were more vulnerable than the hormone sensitive LNCaP cells. The IC50 values for oleic (4), elaidic (5) and docosahexaenoic acid (8) conjugates were 20.2 µM, 17.8 µM and 16.5 µM, respectively, in DU-145 cells, whereas in LNCaP cells IC50 exceeded 20 µM. The strong conjugate cytotoxicity was confirmed in the LDH test, the highest (70.8%) for compound (5) and 64.2% for compound (8) in DU-145 cells. This effect was weaker for LNCaP cells (around 60%). The cytotoxic effect of unconjugated ciprofloxacin and fatty acids was weaker. The early apoptosis was predominant in LNCaP while in DU-145 cells both early and late apoptosis was induced. The tested conjugates decreased IL-6 release in both cancer cell lines by almost 50%. Proteomic analysis indicated influence of the ciprofloxacin conjugates on lipid metabolic proteins in prostatic cancer. Conclusion: Our findings suggested the cytotoxic potential of ciprofloxacin conjugates with reduction in proteins involved in prostate cancer progress.


2022 ◽  
Author(s):  
Maria Fernanda Fernandes ◽  
John Zewen Chan ◽  
Chia Chun Joey Hung ◽  
Michelle Victoria Tomczewski ◽  
Robin Elaine Duncan

Aims: To study effects on cellular innate immune responses to novel genes ORF8 and ORF10, and the more conserved Membrane protein (M protein) from the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes COVID-19, either alone, or in combination with cannabidiol (CBD). Main Methods: HEK293 cells were transfected with a control plasmid, or plasmids expressing ORF8, ORF10, or M protein, and assayed for cell number and markers of apoptosis at 24 h, and expression of interferon and interferon-stimulated genes at 14 h. Key findings: A significant reduction in cell number, and increase in early and late apoptosis, was found after 24 h in cells where expression of viral genes was combined with 1-2 μM CBD treatment, but not in control-transfected cells treated with CBD, or in cells expressing viral genes but treated only with vehicle. CBD (2 μM) augmented expression of IFNγ, IFNλ1 and IFNλ2/3, as well as the 2'-5'-oligoadenylate synthetase (OAS) family members OAS1, OAS2, OAS3, and OASL, in cells expressing ORF8, ORF10, and M protein. CBD also augmented expression of these genes in control cells not expressing viral genes, without enhancing apoptosis. Significance: Our results demonstrate a poor ability of HEK293 cells to respond to SARS-CoV-2 genes alone, but suggest an augmented innate anti-viral response to these genes in the presence of CBD. Furthermore, our results indicate that CBD may prime components of the innate immune system, increasing readiness to respond to viral infection without activating apoptosis, and therefore could be studied for potential in prophylaxis.


Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7305
Author(s):  
Nonhlakanipho F. Sangweni ◽  
Phiwayinkosi V. Dludla ◽  
Nireshni Chellan ◽  
Lawrence Mabasa ◽  
Jyoti R. Sharma ◽  
...  

Although numerous studies have demonstrated the biological and multifaceted nature of dimethyl sulfoxide (DMSO) across different in vitro models, the direct effect of “non-toxic” low DMSO doses on cardiac and cancer cells has not been clearly explored. In the present study, H9c2 cardiomyoblasts and MCF-7 breast cancer cells were treated with varying concentrations of DMSO (0.001–3.7%) for 6 days. Here, DMSO doses < 0.5% enhanced the cardiomyoblasts respiratory control ratio and cellular viability relative to the control cells. However, 3.7% DMSO exposure enhanced the rate of apoptosis, which was driven by mitochondrial dysfunction and oxidative stress in the cardiomyoblasts. Additionally, in the cancer cells, DMSO (≥0.009) led to a reduction in the cell’s maximal respiratory capacity and ATP-linked respiration and turnover. As a result, the reduced bioenergetics accelerated ROS production whilst increasing early and late apoptosis in these cells. Surprisingly, 0.001% DMSO exposure led to a significant increase in the cancer cells proliferative activity. The latter, therefore, suggests that the use of DMSO, as a solvent or therapeutic compound, should be applied with caution in the cancer cells. Paradoxically, in the cardiomyoblasts, the application of DMSO (≤0.5%) demonstrated no cytotoxic or overt therapeutic benefits.


Materials ◽  
2021 ◽  
Vol 14 (21) ◽  
pp. 6435
Author(s):  
Miguel Cardoso ◽  
Ana Coelho ◽  
Carlos Miguel Marto ◽  
Ana Cristina Gonçalves ◽  
Anabela Paula ◽  
...  

This study aimed to assess the cytotoxicity of commercially available adhesive strategies—etch-and-rinse (Adper™ Scotchbond™ 1 XT, 3M ESPE, St. Paul, MN, USA, SB1), self-etch (Clearfil™ SE Bond 2, Kuraray Noritake Dental Inc., Tokyo, Japan, CSE), and universal (Scotchbond™ Universal, 3M Deutschland GmbH, Neuss, Germany, SBU). MDPC-23 cells were exposed to adhesives extracts in different concentrations and exposure times. To access cell metabolic activity, viability, types of cell death, and cell cycle, the MTT assay, SRB assay, double labeling with annexin V and propidium iodide, and labeling with propidium iodide/RNAse were performed, respectively. Cultures were stained with May-Grünwald Giemsa for qualitative cytotoxicity assessment. The SB1, CSE, and SBU extracts determined a significant reduction in cell metabolism and viability. This reduction was higher for prolonged exposures, even for less concentrated extracts. CSE extracts significantly reduced the cell’s metabolic activity at higher concentrations (50% and 100%) from 2 h of exposure. After 24 and 96 h, a metabolic activity reduction was verified for all adhesives, even at lower concentrations. These changes were dependent on the adhesive, its concentration, and the incubation time. Regarding cell viability, SBU extracts were the least cytotoxic, and CSE was significantly more cytotoxic than SB1 and SBU. The adhesives determined a reduction in viable cells and an increase in apoptotic, late apoptosis/necrosis, and necrotic cells. Moreover, on cultures exposed to SB1 and CSE extracts, a decrease in the cells in S and G2/M phases and an increase in the cells in G0/G1 phase was observed. Exposure to SBU led to an increase of cells in the S phase. In general, all adhesives determined cytotoxicity. CSE extracts were the most cytotoxic and were classified as having a higher degree of reactivity, leading to more significant inhibition of cell growth and destruction of the cell’s layers.


Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4724
Author(s):  
Ali H. Abu Almaaty ◽  
Nermeen A. Elgrahy ◽  
Eman Fayad ◽  
Ola A. Abu Ali ◽  
Ahmed R. E. Mahdy ◽  
...  

A new series of hybrid molecules containing cinnamic acid and 2-quinolinone derivatives were designed and synthesized. Their structures were confirmed by 1H-NMR, 13C-NMR and mass analyses. All the synthesized hybrid molecules were assessed for their in vitro antiproliferative activity against more than one cancer cell lines. Compound 3-(3,5-dibromo-7,8-dihydroxy-4-methyl-2-oxoquinolin-1(2H)-ylamino)-3-phenylacrylic acid (5a) with IC50 = 1.89 μM against HCT-116 was proved to the most potent compound in this study, as compared to standard drug staurosporin. DNA flow cytometry assay of compound 5a revealed G2/M phase arrest and pre-G1 apoptosis. Annexin V-FITC showed that the percentage of early and late apoptosis was increased. The results of topoisomerase enzyme inhibition activity showed that the hybrid molecule 5a displays potent inhibitory activity compared with control.


Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1171
Author(s):  
Violeta Popovici ◽  
Elena Matei ◽  
Georgeta Camelia Cozaru ◽  
Mariana Aschie ◽  
Laura Bucur ◽  
...  

Nowadays, numerous biomedical studies performed on natural compounds and plant extracts aim to obtain highly selective pharmacological activities without unwanted toxic effects. In the big world of medicinal plants, Usnea barbata (L) F.H. Wigg (U. barbata) and usnic acid (UA) are well-known for their therapeutical properties. One of the most studied properties is their cytotoxicity on various tumor cells. This work aims to evaluate their cytotoxic potential on normal blood cells. Three dry U. barbata extracts in various solvents: ethyl acetate (UBEA), acetone (UBA), and ethanol (UBE) were prepared. From UBEA we isolated usnic acid with high purity by semipreparative chromatography. Then, UA, UBA, and UBE dissolved in 1% dimethyl sulfoxide (DMSO) and diluted in four concentrations were tested for their toxicity on human blood cells. The blood samples were collected from a healthy non-smoker donor; the obtained blood cell cultures were treated with the tested samples. After 24 h, the cytotoxic effect was analyzed through the mechanisms that can cause cell death: early and late apoptosis, caspase 3/7 activity, nuclear apoptosis, autophagy, reactive oxygen species (ROS) level and DNA damage. Generally, the cytotoxic effect was directly proportional to the increase of concentrations, usnic acid inducing the most significant response. At high concentrations, usnic acid and U. barbata extracts induced apoptosis and DNA damage in human blood cells, increasing ROS levels. Our study reveals the importance of prior natural products toxicity evaluation on normal cells to anticipate their limits and benefits as potential anticancer drugs.


2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Jasem Saki ◽  
Khalil Saki ◽  
Reza Arjmand

Background: The first drug for the treatment of leishmaniasis is pentavalent antimony compounds which have great side effects. Objectives: This study aimed to assess apoptosis induction by HESA-A, an herbal marine compound in Leishmania major promastigotes. Methods: Leishmania major promastigotes were treated with HESA-A in different increasing concentrations ranged 1.625 - 120 µg/mL, and amphotericin B and the phenomenon of apoptosis in the parasite were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, and DNA fragmentation tests. Results: The IC50 value of the compound and amphotericin B at 72 h were estimated at 2.81 µg/mL and 40 µg/mL, respectively. After 72 h of the adjacency of Leishmania major promastigotes with IC50 dose (2.81 µg/mL), the percentage of promastigotes in early and late apoptosis phases in the treated group was 5.4% and 60.4%, respectively. DNA fragmentation of Leishmania major promastigotes treated with 2.81 µg/mL for 72 h was observed. Conclusions: HESA-A, with significant induction of apoptosis in Leishmania major promastigotes, can be plausible in the treatment of cutaneous Leishmaniasis.


Toxins ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 476
Author(s):  
Diego Becker Borin ◽  
Karen Castrejón-Arroyo ◽  
Alain Cruz-Nolasco ◽  
Miguel Peña-Rico ◽  
Michele Sagrillo Rorato ◽  
...  

The protein A13-2 was obtained from Bacillus thuringiensis strains isolated from the Papaloapan watershed region (Oaxaca, Mexico). The cytotoxic activity of parasporal inclusions was studied against breast cancer cell line (MCF-7) and normal cell (human peripheral blood mononuclear cells). The MTT, the formation of reactive species, nitric oxide, free cell DNA, and the type of death cellular were assessed. The protein A13-2 shows the highest cytotoxic activity against MCF-7 (13% cell viability at 6 µg/mL), the extracellular DNA increases, and it shows no stress for reactive species or nitric oxide. Besides, the A13-2 parasporin shows no toxicity to peripheral blood mononuclear cells, and it does not generate changes in nitric oxide levels or free cell DNA. Due to that, the cytotoxic effect of A13-2 was specific for MCF-7, and it does not affect normal cells. According to microscopy and flow cytometry, A13-2 parasporin leads to the death of MCF-7 cells by late apoptosis together with necrosis and without allowing the triggering of the survival mechanisms. When analyzed together, our results show for the first time that the A13-2 protein isolated from Mexican strains of B. thuringiensis preferentially kills MCF- 7 (cancer cells) over HEK 293 and PBMC cell lines (normal cells), thus representing a promising alternative for the treatment of cancer breast.


2021 ◽  
Author(s):  
Layla Adnan AbdulJabar ◽  
Ali AlShawi ◽  
Dakhil Zughayir Mutlaq

Abstract MTT assay and flowcytometry analysis were used to examine the anti-liver (HepG2) and anti-breast cancer (MCF-7) activities of twelve compounds derived from 2-thioxo-4-imidazolidine. The compounds 5a-h and 7f demonstrated significant anticancer activity against breast cancer cells, while the compounds 5a, ab, and 5d-h demonstrated significant anticancer activity against liver cancer cells, with varying IC50 values as compared to Cisplatin as the positive control. Among these compounds, we chose 5a, 5d, and 5h to detect cell cycle phases and late apoptosis. Compound 5a arrested MCF-7 cells in the S phase, while compound 5d arrested cells in the G1 phase. Compound 5a arrested S phase HepG2 cells, compound 5d arrested S phase cells, and compound 5h arrested G2 phase HepG2 cells. Compound 5a had a higher ratio of late apoptosis than compounds 5d and 5h on both cancer cells. Finally, the development of these compounds as new anti-breast and anti-liver agents warrants further research to understand the mechanism of action, especially against breast cancer.


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