IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
DIMES University of Genova, Genoa, Italy.
Invest New Drugs. 2022 Dec;40(6):1185-1193. doi: 10.1007/s10637-022-01294-8. Epub 2022 Aug 17.
Macrocyclic compounds meso-(p-acetamidophenyl)-calix[4]pyrrole and meso-(m-acetamidophenyl)-calix[4]pyrrole have previously been reported to exhibit cytotoxic properties towards lung cancer cells. Here, we report pre-clinical in vitro and in vivo studies showing that these calixpyrrole derivatives can inhibit cell growth in both PC3 and DU145 prostatic cancer cell lines. We explored the impact of these compounds on programmed cell death, as well as their ability to inhibit cellular invasion. In this study we have demonstrated the safety of these macrocyclic compounds by cytotoxicity tests on ex-vivo human peripheral blood mononuclear cells (PBMCs), and by in vivo subcutaneous administration. Preliminary in vivo tests demonstrated no hepato-, no nephro- and no genotoxicity in Balb/c mice compared to controls treated with cisplatin. These findings suggest these calixpyrroles might be novel therapeutic tools for the treatment of prostate cancer and of particular interest for the treatment of androgen-independent castration-resistant prostate cancer.
先前有报道称大环化合物间-（对乙酰氨基苯基）-杯[4]吡咯和间-（间乙酰氨基苯基）-杯[4]吡咯对肺癌细胞具有细胞毒性。在这里，我们报告了临床前体外和体内研究表明，这些杯吡咯衍生物可以抑制 PC3 和 DU145 前列腺癌细胞系的细胞生长。我们探讨了这些化合物对程序性细胞死亡的影响，以及它们抑制细胞侵袭的能力。在这项研究中，我们通过对离体人外周血单核细胞（PBMCs）的细胞毒性试验以及通过体内皮下给药证明了这些大环化合物的安全性。与用顺铂治疗的对照组相比，初步体内试验表明这些化合物在 Balb/c 小鼠中没有肝毒性、肾毒性和遗传毒性。这些发现表明，这些杯吡咯可能是治疗前列腺癌的新型治疗工具，特别是对治疗雄激素非依赖性去势抵抗性前列腺癌具有特别的意义。
