In vitro and in vivo growth inhibitory activities of cryptolepine hydrate against several Babesia species and Theileria equi

Coumermycin A1, a coumarin antibiotic, has anticancer, antibacterial, antiviral, and antimalarial activities. We aimed to evaluate the anti-thielerial and anti-babesial activity of coumermycin A1 in mice in vivo. Coumermycin A1 efficacy was determined by the transcription of DNA gyrase, a type II DNA topoisomerase using reverse transcriptase-polymerase chain reaction (RT-PCR) transcription. Coumermycin A1 significantly inhibited the development of preliminary parasitemia (1%). Theileria equi and the Babesia species B. bigemina, B. bovis, and B. caballi were observed with IC50 values of 80, 70, 57, and 65 nM, respectively. Their development was remarkably inhibited at observed concentrations of 10, 25, 50, and 100µM for the studied organisms T. equi, and the Babesia species B. caballi, B. bovis and B. bigemina, respectively. In the subsequent viability test, parasite re-growth was suppressed at 100µM for B. bigemina and B. bovis and at 50 µM for B. caballi and T. equi. Coumermycin A1 Treatment of B. bovis cultures with Coumermycin A1 completely suppressed the transcription of the DNA gyrase subunits B and A genes. In BALB/c mice, the development of Babesia microti was inhibited by 70.73% using 5 mg/kg of Coumermycin A1.

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"Reverse" and "Symmetrical" Analogues of Actinomycin D: Matabolic Actication and in Vitro and in Vivo Tumor Growth Inhibitory Activities

Journal of Medicinal Chemistry ◽

10.1021/jm50001a015 ◽

1985 ◽

Vol 28 (5) ◽

pp. 620-628 ◽

Cited By ~ 7

Author(s):

Sisir K. Sengupta ◽

Christinne Kelly ◽

Raj K. Sehgal

Keyword(s):

Tumor Growth ◽

Actinomycin D ◽

Growth Inhibitory ◽

Inhibitory Activities

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Evaluation of The In Vitro And In Vivo Inhibitory Effects of Enrofloxacin On the Growth of Babesia Species and Theileria Equi

10.31487/j.dda.2019.01.02 ◽

2019 ◽

pp. 1-6

Author(s):

Ikuo Igarashi ◽

Naoaki Yokoyama ◽

Akram Salama ◽

Amer AbdEl-Aziz ◽

Mahmoud AbouLaila ◽

...

Keyword(s):

Dose Rate ◽

Inhibitory Effect ◽

Babesia Microti ◽

Babesia Species ◽

Mice Model ◽

Inhibitory Effects ◽

Theileria Equi ◽

Diminazene Aceturate

Objectives: Enrofloxacin, a fluoroquinolone antibiotic, is an inhibitor of prokaryotic topoisomerase II with antibacterial and antiparasitic activities. The study aimed to evaluate the inhibitory effect of enrofloxacin on Babesia species and Theileria equi in vitro and in vivo. Methods: The inhibitory effects of enrofloxacin were evaluated in vitro cultures using in vitro inhibition assay of three Babesia species and Theileria equi; furthermore, the in vivo inhibitory effect of enrofloxacin was evaluated in the mice model of Babesia microti. Results: The IC50 values of enrofloxacin were 4.9, 4.5, 4, and 3.9 nM for B. bovis, B. bigemina, B. caballi, and B. equi, respectively. Enrofloxacin at a dose rate of 10 mg/kg resulted in a 92.9 % inhibition of Babesia microti growth in BALB/c mice. Combination therapy of enrofloxacin at a dose rate of 5 mg/kg with diminazene aceturate at a dose rate of 12.5 mg/kg resulted in 93.83 % inhibition of Babesia microti growth in BALB/c mice. Conclusions: Enrofloxacin might be used for drug therapy in babesiosis.

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ChemInform Abstract: “REVERSE” AND “SYMMETRICAL” ANALOGS OF ACTINOMYCIN D: METABOLIC ACTIVATION AND IN VITRO AND IN VIVO TUMOR GROWTH INHIBITORY ACTIVITIES

Chemischer Informationsdienst ◽

10.1002/chin.198534246 ◽

1985 ◽

Vol 16 (34) ◽

Author(s):

S. K. SENGUPTA ◽

C. KELLY ◽

R. K. SEHGAL

Keyword(s):

Tumor Growth ◽

Actinomycin D ◽

Metabolic Activation ◽

Growth Inhibitory ◽

Inhibitory Activities

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Regeneration linked miRNA modify tumor phenotype and can enforce multi-lineage growth arrest in vivo

Scientific Reports ◽

10.1038/s41598-021-90009-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Siamak Salehi ◽

Oliver D. Tavabie ◽

Augusto Villanueva ◽

Julie Watson ◽

David Darling ◽

...

Keyword(s):

Cell Proliferation ◽

Growth Inhibition ◽

Tumor Aggressiveness ◽

Novel Treatment ◽

Tumor Phenotype ◽

Aggressive Tumor ◽

In Vivo Growth ◽

Regulation Of Regeneration

AbstractRegulated cell proliferation is an effector mechanism of regeneration, whilst dysregulated cell proliferation is a feature of cancer. We have previously identified microRNA (miRNA) that regulate successful and failed human liver regeneration. We hypothesized that these regulators may directly modify tumor behavior. Here we show that inhibition of miRNAs -503 and -23a, alone or in combination, enhances tumor proliferation in hepatocyte and non-hepatocyte derived cancers in vitro, driving more aggressive tumor behavior in vivo. Inhibition of miRNA-152 caused induction of DNMT1, site-specific methylation with associated changes in gene expression and in vitro and in vivo growth inhibition. Enforced changes in expression of two miRNA recapitulating changes observed in failed regeneration led to complete growth inhibition of multi-lineage cancers in vivo. Our results indicate that regulation of regeneration and tumor aggressiveness are concordant and that miRNA-based inhibitors of regeneration may constitute a novel treatment strategy for human cancers.

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Trichostatin A downregulates bromodomain and extra-terminal proteins to suppress osimertinib resistant non-small cell lung carcinoma

Cancer Cell International ◽

10.1186/s12935-021-01914-y ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yuting Meng ◽

Xixi Qian ◽

Li Zhao ◽

Nan Li ◽

Shengjie Wu ◽

...

Keyword(s):

Trichostatin A ◽

Small Cell Lung Carcinoma ◽

Cell Types ◽

Inhibitory Effects ◽

Cell Lung Carcinoma ◽

Growth Inhibitory ◽

Terminal Proteins ◽

P Cells

Abstract Background The third-generation epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have shown significant therapeutic effects on patients with non-small cell lung carcinoma (NSCLC) who carry active EGFR mutations, as well as those who have developed acquired resistance to the first-generation of EGFR-TKIs due to the T790M mutation. However, most patients develop drug resistance after 8–10 months of treatment. Currently, the mechanism has not been well clarified, and new therapeutic strategies are urgently needed. Methods Osimertinib resistant cell lines were established by culturing sensitive cells in chronically increasing doses of osimertinib. The anticancer effect of reagents was examined both in vitro and in vivo using the sulforhodamine B assay and a xenograft mouse model. The molecular signals were detected by western blotting. The combination effect was analyzed using CompuSyn software. Results We found that bromodomain and extra-terminal proteins (BETs) were upregulated in osimertinib resistant (H1975-OR) cells compared with those in the paired parental cells (H1975-P), and that knockdown of BETs significantly inhibited the growth of H1975-OR cells. The BET inhibitor JQ1 also exhibited stronger growth-inhibitory effects on H1975-OR cells and a greater expression of BETs and the downstream effector c-Myc than were observed in H1975-P cells. The histone deacetylase (HDAC) inhibitor trichostatin A (TSA) showed stronger growth suppression in H1975-OR cells than in H1975-P cells, but vorinostat, another HDAC inhibitor, showed equal inhibitory efficacy in both cell types. Consistently, downregulation of BET and c-Myc expression was greater with TSA than with vorinostat. TSA restrained the growth of H1975-OR and H1975-P xenograft tumors. The combination of TSA and JQ1 showed synergistic growth-inhibitory effects in parallel with decreased BET and c-Myc expression in both H1975-OR and H1975-P cells and in xenograft nude mouse models. BETs were not upregulated in osimertinib resistant HCC827 cells compared with parental cells, while TSA and vorinostat exhibited equal inhibitory effects on both cell types. Conclusion Upregulation of BETs contributed to the osimertinib resistance of H1975 cells. TSA downregulated BET expression and enhanced the growth inhibitory effect of JQ1 both in vitro and in vivo. Our findings provided new strategies for the treatment of osimertinib resistance.

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Asian ginseng extract inhibits in vitro and in vivo growth of mouse lewis lung carcinoma via modulation of ERK-p53 and NF-κB signaling

Journal of Cellular Biochemistry ◽

10.1002/jcb.22778 ◽

2010 ◽

Vol 111 (4) ◽

pp. 899-910 ◽

Cited By ~ 38

Author(s):

Vincent Kam Wai Wong ◽

Simon Shiu Fai Cheung ◽

Ting Li ◽

Zhi-Hong Jiang ◽

Jing-Rong Wang ◽

...

Keyword(s):

Lung Carcinoma ◽

Lewis Lung Carcinoma ◽

Lewis Lung ◽

Ginseng Extract ◽

In Vivo Growth

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In VivoEfficacy of Anuran Trypsin Inhibitory Peptides against Staphylococcal Skin Infection and the Impact of Peptide Cyclization

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.04324-14 ◽

2015 ◽

Vol 59 (4) ◽

pp. 2113-2121 ◽

Cited By ~ 9

Author(s):

U. Malik ◽

O. N. Silva ◽

I. C. M. Fensterseifer ◽

L. Y. Chan ◽

R. J. Clark ◽

...

Keyword(s):

Antimicrobial Agents ◽

Cyclic Peptide ◽

Sequence Similarity ◽

Infection Model ◽

Content Type ◽

Wide Range ◽

Inhibitory Activities ◽

The Impact

ABSTRACTStaphylococcus aureusis a virulent pathogen that is responsible for a wide range of superficial and invasive infections. Its resistance to existing antimicrobial drugs is a global problem, and the development of novel antimicrobial agents is crucial. Antimicrobial peptides from natural resources offer potential as new treatments against staphylococcal infections. In the current study, we have examined the antimicrobial properties of peptides isolated from anuran skin secretions and cyclized synthetic analogues of these peptides. The structures of the peptides were elucidated by nuclear magnetic resonance (NMR) spectroscopy, revealing high structural and sequence similarity with each other and with sunflower trypsin inhibitor 1 (SFTI-1). SFTI-1 is an ultrastable cyclic peptide isolated from sunflower seeds that has subnanomolar trypsin inhibitory activity, and this scaffold offers pharmaceutically relevant characteristics. The five anuran peptides were nonhemolytic and noncytotoxic and had trypsin inhibitory activities similar to that of SFTI-1. They demonstrated weakin vitroinhibitory activities againstS. aureus, but several had strong antibacterial activities againstS. aureusin anin vivomurine wound infection model. pYR, an immunomodulatory peptide fromRana sevosa, was the most potent, with complete bacterial clearance at 3 mg · kg−1. Cyclization of the peptides improved their stability but was associated with a concomitant decrease in antimicrobial activity. In summary, these anuran peptides are promising as novel therapeutic agents for treating infections from a clinically resistant pathogen.

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Regulation of the MST1 kinase by autophosphorylation, by the growth inhibitory proteins, RASSF1 and NORE1, and by Ras

Biochemical Journal ◽

10.1042/bj20040025 ◽

2004 ◽

Vol 381 (2) ◽

pp. 453-462 ◽

Cited By ~ 229

Author(s):

Maria PRASKOVA ◽

Andrei KHOKLATCHEV ◽

Sara ORTIZ-VEGA ◽

Joseph AVRUCH

Keyword(s):

Mammalian Cells ◽

Kb Cells ◽

Serum Stimulation ◽

Growth Inhibitory ◽

Catalytic Fragment ◽

Endogenous Substrates ◽

Gc Protein ◽

Caax Motif

MST1 (mammalian Sterile20-like 1) and MST2 are closely related Class II GC (protein Ser/Thr) kinases that initiate apoptosis when transiently overexpressed in mammalian cells. In the present study, we show that recombinant MST1/2 undergo a robust autoactivation in vitro, mediated by an intramolecular autophosphorylation of a single site [MST1(Thr183)/MST2(Thr180)] on the activation loop of an MST dimer. Endogenous full-length MST1 is activated by a variety of stressful stimuli, accompanied by the secondary appearance of a 36 kDa Thr183-phosphorylated, caspase-cleaved catalytic fragment. Recombinant MST1 exhibits only 2–5% activation during transient expression; endogenous MST1 in the cycling HeLa or KB cells has a similar low fractional activation, but 2 h incubation with okadaic acid (1 μM) results in 100% activation. Endogenous MST1 immunoprecipitated from KB cells is specifically associated with substoichiometric amounts of the growth inhibitory polypeptides RASSF1A and NORE1A (novel Ras effector 1A; a Ras-GTP-binding protein). Co-expression of RASSF1A, RASSF1C, NORE1A and NORE1B with MST1 markedly suppresses MST1(Thr183) phosphorylation in vivo and abolishes the ability of MST1 to undergo Mg-ATP-mediated autoactivation in vitro; direct addition of purified NORE1A in vitro also inhibits MST1 activation. In contrast, co-transfection of MST1 with NORE1A modified by the addition of a C-terminal CAAX motif results in a substantial increase in MST1(Thr183) phosphorylation, as does fusion of a myristoylation motif directly on to the MST1 N-terminus. Moreover, MST1 polypeptides, bound via wild-type NORE1A to Ras(G12V) (where G12V stands for Gly12→Val), exhibit higher Thr183 phosphorylation compared with MST1 bound to NORE1A alone. Nevertheless, serum stimulation of KB cells does not detectably increase the activation state of endogenous MST1 or MST2 despite promoting the recruitment of the endogenous NORE1–MST1 complex to endogenous Ras. We propose that the NORE1/RASSF1 polypeptides, in addition to their role in maintaining the low activity of MST1 in vivo, direct MST1 to sites of activation and perhaps co-localization with endogenous substrates.

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