A recent study published in Inorganic Chemistry explored the potential of azolato-bridged dinuclear platinum(II) complexes in treating prostate cancer.

The research team, led by Associate Professor Yoshihisa Hirota and Professor Seiji Komeda, focused on a complex called 5-H-Y ({ cis -Pt(NH3)2}2(μ-OH)(μ-tetrazolato- N2 , N3 )2) as a potential 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.

According to Dr. Hirota, the first platinum-based drug, cisplatin, has a powerful effect on cancer by binding to nuclear DNA; however, it also affects normal cells and causes serious side effects. The study found that some azolato-bridged complexes inhibit AR signaling, which is crucial for prostate cancer proliferation, in addition to the anticancer effect initiated by the DNA-binding.

The team used several methods to evaluate AR dynamics and therapeutic effects in LNCaP prostate cancer cells, including cell viability, gene expression, and protein analyses, and immunofluorescence staining.

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. Additionally, 5-H-Y effectively suppressed the expression of AR-responsive genes, such as PSA and TMPRSS2, and induced apoptosis in AR-overexpressing cells. Immunofluorescence analysis confirmed that 5-H-Y promoted chromatin fragmentation, a hallmark of apoptosis, with greater efficacy at higher concentrations.

Importantly, 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 have the potential to effectively inhibit cancer progression while minimizing side effects.

Overall, the study suggests that dinuclear platinum(II) complexes may offer a more targeted approach to treating prostate cancer by inhibiting AR-mediated cell growth and survival.

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