New Platinum Complex May Have Strong Antiproliferative Effects in Prostate Cancer Cases: Study Suggests
In a recent study published in the journal Inorganic Chemistry, a team of researchers explored the potential of azolato-bridged dinuclear platinum(II) complexes (azolato-bridged complexes) in treating prostate cancer. The study particularly focused on a complex called 5-H-Y ([{cis-Pt(NH3)2}2(μ-OH)(μ-tetrazolato-N2,N3)](ClO4)2) as an alternative to cisplatin. These complexes are characterized by their water solubility and promising antiproliferative effects against prostate cancer cell lines, with minimal toxicity compared to traditional platinum-based drugs.
The team used a variety of methods to evaluate androgen receptor dynamics and therapeutic effects in LNCaP prostate cancer cells. They utilized azolato-bridged complexes, cisplatin, and the androgen receptor antagonist KW-365 to explore their efficacy and performed cell viability, gene expression, and protein analyses. Additionally, the team employed immunofluorescence staining to visualize AR expression and evaluated apoptosis (programmed cell death), cell cycle distribution, and nuclear platinum accumulation.
The results showed that 5-H-Y exhibited significantly stronger cytotoxic effects than cisplatin, with a low half-maximal inhibitory concentration for dihydrotestosterone (DHT)-induced cell proliferation. Moreover, 5-H-Y effectively suppressed the expression of androgen receptor-responsive genes. Immunofluorescence analysis confirmed that 5-H-Y promoted chromatin fragmentation, a hallmark of apoptosis, with greater efficacy observed at higher concentrations.
Despite its high antiproliferative activity, however, 5-H-Y demonstrated lower acute toxicity in vivo compared to other platinum complexes, making it a promising candidate for further development. “The azolato-bridged complexes used in this research are expected to play a key role in developing new treatments for advanced prostate cancer. For patients whose cancer has become resistant to conventional therapies, these complexes have the potential to effectively inhibit cancer progression with multi-layered attack while minimizing side effects. Our approach could thus expand treatment options for prostate cancer and improve the patient’s quality of life” says Associate Professor Yoshihisa Hirota from Shibaura Institute of Technology (SIT)
Reference: Arai, T., Oshima, M., Uemura, M., Matsunaga, T., Ashizawa, T., Suhara, Y., ... & Hirota, Y. (2024). Azolato-Bridged Dinuclear Platinum (II) Complexes Exhibit Androgen Receptor-Mediated Anti-Prostate Cancer Activity. Inorganic Chemistry, 63(44), 20951-20963.
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