Subcellular localization and photodynamic activity of Photodithazine (glucosamine salt of chlorin e6) in murine melanoma B16-F10: an in vitro and in vivo study

Introduction of α-cyano α,β-unsaturated carbonyl moiety into natural cyclic compounds markedly improves their bioactivities, including inhibitory potential against tumor growth and metastasis. Previously, we showed that cyano enone-bearing derivatives of 18βH-glycyrrhetinic (GA) and deoxycholic acids displayed marked cytotoxicity in different tumor cell lines. Moreover, GA derivative soloxolone methyl (SM) was found to induce ER stress and apoptosis in tumor cells in vitro and inhibit growth of carcinoma Krebs-2 in vivo. In this work, we studied the effects of these compounds used in non-toxic dosage on the processes associated with metastatic potential of tumor cells. Performed screening revealed SM as a hit compound, which inhibits motility of murine melanoma B16 and human lung adenocarcinoma A549 cells and significantly suppresses colony formation of A549 cells. Further study showed that SM effectively blocked transforming growth factor β (TGF-β)-induced epithelial-mesenchymal transition (EMT) of A549 cells: namely, inhibited TGF-β-stimulated motility and invasion of tumor cells as well as loss of their epithelial characteristics, such as, an acquisition of spindle-like phenotype, up- and down-regulation of mesenchymal (vimentin, fibronectin) and epithelial (E-cadherin, zona occludens-1 (ZO-1)) markers, respectively. Network pharmacology analysis with subsequent verification by molecular modeling revealed that matrix metalloproteinases MMP-2/-9 and c-Jun N-terminal protein kinase 1 (JNK1) can be considered as hypothetical primary targets of SM, mediating its marked anti-EMT activity. The inhibitory effect of SM on EMT revealed in vitro was further confirmed in a metastatic model of murine B16 melanoma: SM was found to effectively block metastatic dissemination of melanoma B16 cells in vivo, increase expression of E-cadherin and suppress expression of MMP-9 in lung metastatic foci. Altogether, our data provided valuable information for a better understanding of the antitumor activity of cyano enone-bearing semisynthetic compounds and revealed SM as a promising anti-metastatic drug candidate.

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Photodynamic activity of chlorin e6 and chlorin e6 ethylenediamide in vitro and in vivo

Journal of Photochemistry and Photobiology B Biology ◽

10.1016/1011-1344(92)80039-x ◽

1992 ◽

Vol 13 (1) ◽

pp. 51-57 ◽

Cited By ~ 24

Author(s):

G.P. Gurinovich ◽

T.E. Zorina ◽

S.B. Melnov ◽

N.I. Melnova ◽

I.F. Gurinovich ◽

...

Keyword(s):

Chlorin E6 ◽

Photodynamic Activity

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Antitumor effect of a pyrazolone-based-complex [Cu(PMPP-SAL)(EtOH)] against murine melanoma B16 cell in vitro and in vivo

Acta Pharmaceutica ◽

10.2478/acph-2020-0040 ◽

2020 ◽

Vol 70 (4) ◽

pp. 561-575

Author(s):

Ayipairi Abula ◽

Jing Zhao ◽

Guancheng Xu ◽

Yijie Li ◽

Surong Sun

Keyword(s):

Growth Factor ◽

Antitumor Effect ◽

Therapeutic Potential ◽

Control Group ◽

Murine Melanoma ◽

Melanoma B16 ◽

Induction Of Apoptosis ◽

Endothelial Growth Factor

AbstractPyrazolone-based derivative metal complexes were reported to have cytotoxicity in some tumor cells. In this study, the antitumor effect of [Cu(PMPP-SAL)(EtOH)] (PMPP-SAL = N-(1-phenyl-3-methyl-4-propenylidene-5-pyrazolone)- salicylidene hydrazide anion) in murine melanoma B16 cells in vitro and in vivo was investigated. The results showed that [Cu(PMPP-SAL)(EtOH)] inhibited the survival of B16 cells in vitro, and the IC50 value was superior to cisplatin (DDP) (p < 0.001). B16 cell apoptosis was significantly higher in comparison to the control group (DMSO) (p < 0.01), and cell cycle arrest occurred at the G0/G1 phase. When challenged C57 BL/6J mice were treated with [Cu(PMPPSAL)(EtOH)], a smaller volume of B16 solid tumors were reported than the control group (p < 0.01), with lower positive expression indices of CD 34, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) (p < 0.01). Moreover, the tumor growth was suppressed in mice due to the induction of apoptosis, as detected by the TUNEL assay (p < 0.001). In summary, [Cu(PMPP-SAL)(EtOH)] effectively inhibited the growth of B16 cells in vitro and in vivo due to the induction of apoptosis and the inhibition of intra-tumoral angiogenesis, demonstrating its therapeutic potential in melanoma treatment.

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Faculty Opinions recommendation of A pivotal role for heat shock protein 90 in Ewing sarcoma resistance to anti-insulin-like growth factor 1 receptor treatment: in vitro and in vivo study.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1120094.576229 ◽

2008 ◽

Author(s):

Richard Riedel

Keyword(s):

Growth Factor ◽

Heat Shock ◽

Heat Shock Protein ◽

Ewing Sarcoma ◽

Heat Shock Protein 90 ◽

Pivotal Role ◽

In Vivo Study ◽

Insulin Like Growth Factor

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Biological effect of Egyptian Propolis on BHK cell line and on dental pulp tissue (An In vitro And In vivo study)

Egyptian Dental Journal ◽

10.21608/edj.2018.76780 ◽

2018 ◽

Vol 64 (3) ◽

pp. 2161-2170

Author(s):

Marwa Moussa ◽

Marwa Temirek

Keyword(s):

Cell Line ◽

Dental Pulp ◽

Biological Effect ◽

In Vivo Study ◽

Pulp Tissue ◽

Dental Pulp Tissue

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Formulation and Evaluation of Atorvastatin Calcium-Poly-ε-Caprolactone Nanoparticles Loaded Ocular Inserts for Sustained Release and Antiinflammatory Efficacy

Current Pharmaceutical Biotechnology ◽

10.2174/1389201021666200519133350 ◽

2020 ◽

Vol 21 (15) ◽

pp. 1688-1698

Author(s):

Germeen N.S. Girgis

Keyword(s):

Sustained Release ◽

In Vitro Release ◽

Pluronic F127 ◽

In Vivo Study ◽

Average Weight ◽

Drug Release Profile ◽

Atorvastatin Calcium ◽

Anti Inflammatory

Purpose: The work was performed to investigate the feasibility of preparing ocular inserts loaded with Poly-ε-Caprolactone (PCL) nanoparticles as a sustained ocular delivery system. Methods: First, Atorvastatin Calcium-Poly-ε-Caprolactone (ATC-PCL) nanoparticles were prepared and characterized. Then, the optimized nanoparticles were loaded within inserts formulated with Methylcellulose (MC) and Polyvinyl Alcohol (PVA) by a solvent casting technique and evaluated physically, for in-vitro drug release profile. Finally, an in-vivo study was performed on the selected formulation to prove non-irritability and sustained ocular anti-inflammatory efficacy compared with free drug-loaded ocuserts. Results: The results revealed (ATC-PCL) nanoparticles prepared with 0.5% pluronic F127 were optimized with 181.72±3.6 nm particle size, 0.12±0.02 (PDI) analysis, -27.4± 0.69 mV zeta potential and 62.41%±4.7% entrapment efficiency. Nanoparticles loaded ocuserts manifested compatibility between drug and formulation polymers. Moreover, formulations complied with average weight 0.055±0.002 to 0.143±0.023 mg, and accepted pH. ATC-PCL nanoparticles loaded inserts prepared by 5% MC showed more sustained, prolonged in-vitro release over 24h. In-vivo study emphasized non-irritability, ocular anti-inflammatory effectiveness represented by smaller lid closure scores, and statistically significant lowering in PMN count after 3h. Conclusion: These findings proposed a possibly simple, new and affordable price technique to prepare promising (ATC-PCL) nanoparticles loaded inserts to achieve sustained release with prolonged antiinflammatory efficacy.

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