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Palladium(II) Schiff base complex arrests cell cycle at early stages, induces apoptosis, and reduces Ehrlich solid
Shahd M Hassona1, Entsar A Saad2, Hala A Kiwan1
1Chemistry Department, Faculty of Science, Damietta University, Damietta, 34517, Egypt.
Abstract:
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.
Insights
A novel palladium(II) complex demonstrates significant antitumor and apoptotic activities against Ehrlich carcinoma in vitro and in vivo. This promising cancer therapy candidate shows improved efficacy and safety compared to cisplatin.
Area of Science:
- Medicinal Chemistry
- Pharmacology
- Oncology
Background:
- Existing cancer drugs face challenges with efficacy, drug resistance, and adverse side effects.
- There is a critical need for developing safer and more effective alternative cancer therapies.
Purpose of the Study:
- To investigate the antitumor and apoptotic effects of a palladium(II) 2-hydroxyimino-3-(2-hydrazonopyridyl)-butane complex against Ehrlich carcinoma.
- To evaluate the complex's efficacy and safety in both in vitro and in vivo models.
Main Methods:
- In vitro studies assessed Ehrlich carcinoma (EAC) cell viability, caspase 8 activity, and cell cycle distribution after complex treatment.
- In vivo studies involved EAC-bearing mice treated with varying doses of the complex or cisplatin, monitoring tumor growth, survival, body weight, and blood parameters.
Main Results:
- The palladium(II) complex inhibited EAC cell proliferation, induced apoptosis by increasing caspase 8 activity, and caused G0/G1 cell cycle arrest in vitro.
- In vivo, the complex significantly reduced tumor volume and weight, prolonged median survival time (%ILS), improved body weight gain, and enhanced blood profiles.
- The highest dose of the complex exhibited superior outcomes to cisplatin, with no observed toxicity in normal mice.
Conclusions:
- The palladium(II) complex exhibits potent antiproliferative and antitumor activities, primarily through apoptosis induction.
- This Pd(II) complex represents a promising candidate for cancer therapy, demonstrating favorable efficacy and safety profiles.
- Further studies are warranted to validate these findings and explore clinical applications.
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