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Apoptosis-inducing Effect of a Palladium(II) Complex-[PdCl(terpy)](sac).2H2O] on Ehrlich Ascites Carcinoma (EAC) in
Elif I Ikitimur-Armutak1, Engin Ulukaya2, Ebru Gurel-Gurevin3
1Department of Histology and Embryology, Faculty of Veterinary Medicine, Istanbul University, Istanbul, Turkey.
Background/Aim:
New compounds for cancer treatment are needed due to persistenly unsatisfactory management of cancer. [PdCl(terpy)](sac)·2H2O] (sac=saccharinate, and terpy=2,2':6',2"-terpyridine) is a compound synthesized for this purpose. We investigated its anti-proliferative and pro-apoptotic effects on Ehrlich Ascites Carcinoma (EAC) in vivo.
Materials And Methods:
42 Balb-c female mice were subcutaneously (s.c.) injected with EAC cells (1st day) and then randomly divided into 5 groups: control (0.9% NaCl), complex (2 mg/kg), complex (3 mg/kg) cisplatin (4 mg/kg) and paclitaxel (12.5 mg/kg). On the 5th and 12th day animals were drug administrated. At 14th day, animals were sacrificed. Expression of cell death and/or cell cycle-related markers (Bcl-2, Bax, active caspase-3, p53, PCNA) and apoptosis were investigated immunohisto-chemically. Survival-related markers (Akt, GSK-3β, IGF-1R, IR, IRS-1, p70S6K, PRAS40) were evaluated by luminex analysis.
Results:
Expression of p53, PCNA, Bcl-2 was found decreased (p<0.001) and that of active caspase-3, Bax, and apoptotic cells was found increased (p<0.001) in all groups. The survival-related markers did not show any statistical difference in complex groups.
Conclusion:
The Pd(II)-complex seems to have a strong anticancer activity on EAC by inducing apoptosis via both suppression of proliferation and activation of apoptosis in vivo, similar to the effects of cisplatin and paclitaxel.
Insights
A novel palladium(II) complex demonstrated significant anticancer effects against Ehrlich Ascites Carcinoma (EAC) in mice. This compound effectively suppressed tumor cell proliferation and induced apoptosis, showing promise as a new cancer therapy.
Area of Science:
- Inorganic Chemistry
- Medicinal Chemistry
- Cancer Biology
Background:
- There is a persistent need for novel anticancer agents due to limitations in current cancer management strategies.
- A new palladium(II) complex, [PdCl(terpy)](sac)·2H2O, has been synthesized for potential therapeutic applications.
- The compound utilizes 2,2':6',2''-terpyridine (terpy) and saccharinate (sac) ligands.
Purpose of the Study:
- To investigate the anti-proliferative and pro-apoptotic effects of the synthesized palladium(II) complex.
- To evaluate the efficacy of the compound against Ehrlich Ascites Carcinoma (EAC) in a murine model.
- To compare the compound's activity with established chemotherapy drugs like cisplatin and paclitaxel.
Main Methods:
- Ehrlich Ascites Carcinoma (EAC) cells were implanted in Balb-c female mice.
- Mice were treated with the palladium(II) complex (2 or 3 mg/kg), cisplatin (4 mg/kg), or paclitaxel (12.5 mg/kg), with a control group receiving saline.
- Cell death and cell cycle markers (Bcl-2, Bax, caspase-3, p53, PCNA) were assessed using immunohistochemistry; survival markers were analyzed via Luminex.
Main Results:
- The palladium(II) complex significantly decreased the expression of p53, PCNA, and Bcl-2 (p<0.001).
- Conversely, the expression of active caspase-3, Bax, and the number of apoptotic cells were significantly increased (p<0.001).
- No significant statistical differences were observed in survival-related markers between the complex-treated groups.
Conclusions:
- The palladium(II) complex exhibits potent anticancer activity against EAC in vivo.
- The compound induces apoptosis by suppressing proliferation and activating apoptotic pathways.
- Its mechanism of action appears comparable to that of cisplatin and paclitaxel.
