Apoptotic and anti-proliferative activity of novel platinum complex [Pt((E)-N-((E)-4-hydroxy-3-methoxybenzylidene)-2- (pyridine-2-ylmethylene)hydrazine-1-carbothioamide)] against Ehrlich Ascites carcinoma (EAC) cells in vivo

Abstract Background and Objectives Several platinum complexes have been used in clinical studies to address adverse effects and tumor resistance to cisplatin. Hence, the objective of the current study was to synthesize, characterize, and examine the anticancer activity of a novel platinum complex in EAC cells. Methods A synthetic compound was synthesized from Platinum and Schiff base ligands. The anticancer activity of the complex was tested against EAC cells in Swiss albino mice by monitoring several parameters, such as tumor cell growth, survival time, tumor mass, and hematological profile. Morphological observation and modulation of apoptotic regulatory genes’ expression were used to study its anticancer mechanisms. Results The IUPAC name of the ligand is ((E)-N-((E)-4-hydroxy-3-methoxybenzylidene)-2-(pyridine-2-ylmethylene) hydrazine-1-carbothioamide) [L]. The complex exhibited significant anticancer activity against EAC cells. It showed 45.01% (p < 0.01) and 62.57% (p < 0.001) cell growth inhibition at doses of 2.0 and 5.0 mg/kg/day, respectively, and significantly prolonged survival (30 versus 19 days; p < .01). Also, it reduced (37.1%) tumor weight at 5.0 mg/kg/day on EAC bearing Swiss albino mice. Moreover, EAC-bearing mice receiving the treatment restored blood parameters. It did not exhibit any long-term adverse effects on hematological, biochemical, or tissue parameters in mice. The compound-treated EAC cells showed increased expression of pro-apoptotic genes such as p53, Bax, Cas-3, 9, and decreased expression of anti-apoptotic gene Bcl2, indicating mitochondrial intrinsic pathway activation. Conclusions The compound showed potential anticancer activity by inducing apoptosis; however, further preclinical and clinical research is imperative before using animal and human models.