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Anticancer Properties and Mechanisms of Singly-Protonated Dehydronorcantharidin Silver Coordination Polymer in a
Changkuo Zhou1, Ganyu Wang2, Weiqiang Jing1
1Department of Urology, Qilu Hospital, Shandong University, Jinan, China.
Abstract:
Bladder cancer is the most common malignant urinary system tumor. Chemotherapy is frequently used as a treatment regimen for patients with bladder cancer, however, new and effective drugs for bladder cancer need to be developed. The present study examined the effects and mechanisms of Ag-SP-DNC, a silver and singly-protonated dehydronorcantharidin complex, on bladder cancer in vitro and in vivo. It was identified that Ag-SP-DNC suppressed cell proliferation and induced apoptosis in bladder cancer cells in vitro, a suppression associated with G0/G1 phase arrest and elevated intracellular reactive oxygen species (ROS) levels. Furthermore, Ag-SP-DNC enhanced the cleaved caspase-3 levels, disrupted the mitochondrial transmembrane potential balance, and induced intracellular calcium overload. The Ag-SP-DNC-induced bladder cancer cell apoptosis was significantly decreased following treatment with a broad caspase inhibitor, zVAD-fmk. In addition, treatment of MB49 tumor-bearing mice with Ag-SP-DNC significantly inhibited tumor growth and decreased the anti-apoptosis and cell cycle promotion protein levels in the tumor. The results of the present study suggested that Ag-SP-DNC elicits a strong anticancer effect against bladder cancer, and can therefore be used as a promising treatment for bladder cancer.
Insights
A novel silver complex, Ag-SP-DNC, effectively combats bladder cancer by inhibiting cell growth and promoting apoptosis. This compound shows promise as a new therapeutic agent for bladder cancer treatment.
Area of Science:
- Oncology
- Pharmacology
- Biochemistry
Background:
- Bladder cancer is a prevalent malignancy within the urinary system.
- Current chemotherapy treatments for bladder cancer necessitate the development of novel, more effective drugs.
Purpose of the Study:
- To investigate the anticancer effects and underlying mechanisms of Ag-SP-DNC, a silver and singly-protonated dehydronorcantharidin complex, against bladder cancer.
- To evaluate the efficacy of Ag-SP-DNC both in vitro and in vivo.
Main Methods:
- Assessed Ag-SP-DNC's impact on bladder cancer cell proliferation and apoptosis in vitro.
- Analyzed cell cycle progression, reactive oxygen species (ROS) levels, mitochondrial membrane potential, and intracellular calcium.
- Investigated the role of caspases in Ag-SP-DNC-induced apoptosis using zVAD-fmk.
- Evaluated Ag-SP-DNC's effect on tumor growth in vivo using MB49 tumor-bearing mice.
Main Results:
- Ag-SP-DNC suppressed bladder cancer cell proliferation and induced apoptosis in vitro, linked to G0/G1 phase arrest and increased ROS.
- The compound elevated cleaved caspase-3 levels, disrupted mitochondrial potential, and caused calcium overload.
- Ag-SP-DNC treatment significantly inhibited tumor growth in vivo and reduced levels of anti-apoptotic and cell cycle promoting proteins.
Conclusions:
- Ag-SP-DNC demonstrates significant anticancer activity against bladder cancer.
- The findings suggest Ag-SP-DNC is a potential therapeutic candidate for bladder cancer treatment.
