Acta Pharm. 70 (2020) 561-575

 

full paper

Short communication

 

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

AYIPAIRI ABULA, JING ZHAO, GUANCHENG XU, YIJIE LI and SURONG SUN

sr_sun2005@163.com; sunsrxju@xju.edu.cn

1 Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi 830046, PR China

2 People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830046, PR China

3 Institute of Applied Chemistry, Xinjiang University, Urumqi 830046, PR China

Accepted February 10, 2020

Published online April 10, 2020

 

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 = 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 result 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(PMPP-SAL)(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.

 

Keywords: malignant melanoma, [Cu(PMPP-SAL)(EtOH)], apoptosis, tumor microangiogenesis