Palladium (II) Schiff base complex arrests cell cycle at early stages, induces apoptosis, and reduces Ehrlich solid tumor burden: a new candidate for tumor therapy

Although many cancer drugs are clinically approved, they still suffer from no adequate efficiency or drug resistance, or bad side effects. Therefore, developing safer alternatives of competitive efficiency is needed. This study aimed to investigate, for the first time, the antitumor and apoptotic activities of palladium(II) 2-hydroxyimino-3-(2-hydrazonopyridyl)-butane complex against Ehrlich carcinoma. In vitro, EAC cells were incubated with the complex, and the cells’ viability, caspase 8 activity, and cell cycle changes were evaluated. In vivo, eighty adult female Swiss albino mice were distributed randomly in the following groups (n = 10): Normal, EAC, EAC + Cisplatin, and four groups EAC + Complex as well as Normal + Complex. Bodyweight changes were noted. On day 22 mice were sacrificed. Tumors' volume and weight were recorded. Blood picture was routinely investigated. The median survival time (MST) and percent increase in life span (%ILS) were monitored. In vitro, the complex reduced the %viable EAC cells, increased caspase 8 activity, arrested cell cycle at G0/G1, and reduced G2(M) population indicating antiproliferative and antitumor activities via inducing apoptosis. Treatment with the complex in a dose-dependent mode significantly decreased tumor volume and weight, extended the MST and the %ILS, increased mice body weight gain, and improved the blood indexes. Treatment of EAC-bearing mice with the complex highest dose showed more desirable outcomes than treatment with cisplatin. The Normal + Complex group showed no pathological changes indicating safety. In conclusion, our outcomes recommend the Pd(II) complex as a new optimistic candidate for tumor therapy after further studies for validation.