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

Pyrazolone-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 = -(1-phenyl-3-methyl-4-propenylidene-5-pyrazolone)- salicylidene hydrazide anion) in murine melanoma B16 cells and was investigat...

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Published in:Acta pharmaceutica (Zagreb, Croatia) Vol. 70; no. 4; pp. 561 - 575
Main Authors: Abula, Ayipairi, Zhao, Jing, Xu, Guancheng, Li, Yijie, Sun, Surong
Format: Journal Article
Language:English
Published: Poland Sciendo 01.12.2020
De Gruyter Brill Sp. z o.o., Paradigm Publishing Services
Subjects:
Angiogenesis
Angiogenesis Inhibitors - pharmacology
Animals
Antigens, CD34 - biosynthesis
Antineoplastic Agents - pharmacology
Antitumor activity
Apoptosis
Cadmium
Cell cycle
Cell Survival - drug effects
Cisplatin
Cisplatin - pharmacology
Copper
Cu(PMPP-SAL)(EtOH)
Cytotoxicity
Drug Screening Assays, Antitumor
Fibroblast growth factor 2
G1 phase
Growth factors
malignant melanoma
Melanoma
Melanoma, Experimental - drug therapy
Mice
Mice, Inbred C57BL
Pyrazolones - pharmacology
Solid tumors
Tumor cells
tumor microangiogenesis
Vascular endothelial growth factor
Vascular Endothelial Growth Factor A - biosynthesis
Xenograft Model Antitumor Assays
tumor microangiogenesis
apoptosis
malignant melanoma
Cu(PMPP-SAL)(EtOH)
ISSN:1846-9558, 1330-0075, 1846-9558
Online Access:Get full text
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Summary:Pyrazolone-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 = -(1-phenyl-3-methyl-4-propenylidene-5-pyrazolone)- salicylidene hydrazide anion) in murine melanoma B16 cells and was investigated. The results showed that [Cu(PMPP-SAL)(EtOH)] inhibited the survival of B16 cells , and the value was superior to cisplatin (DDP) ( < 0.001). B16 cell apoptosis was significantly higher in comparison to the control group (DMSO) ( < 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 ( < 0.01), with lower positive expression indices of CD 34, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) ( < 0.01). Moreover, the tumor growth was suppressed in mice due to the induction of apoptosis, as detected by the TUNEL assay ( < 0.001). In summary, [Cu(PMPP-SAL)(EtOH)] effectively inhibited the growth of B16 cells and due to the induction of apoptosis and the inhibition of intra-tumoral angiogenesis, demonstrating its therapeutic potential in melanoma treatment.
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ISSN:1846-9558
1330-0075
1846-9558
DOI:10.2478/acph-2020-0040