Flis Anna, Suchocki Piotr, Królikowska Monika Anna, Suchocka Zofia, Remiszewska Małgorzata, Śliwka Lidia, Książek Iza, Sitarz Karolina, Sochacka Małgorzata, Hoser Grażyna, Anuszewska Elżbieta, Wroczyński Piotr, Jastrzębski Zenon
Department of Bioanalysis and Drugs Analysis, Medical University of Warsaw, Warszawa, Poland.
Department of Bioanalysis and Drugs Analysis, Medical University of Warsaw, Warszawa, Poland; Department of Pharmaceutical Chemistry, National Medicines Institute, Warszawa, Poland.
Pharmacol Rep. 2015 Feb;67(1):1-8. doi: 10.1016/j.pharep.2014.07.017. Epub 2014 Aug 14.
Human prostate cancer (hPCa) is the most commonly diagnosed cancer in elderly men and is the second leading cause of male cancer death. Data from epidemiological, eco-environmental, nutritional prevention and clinical trials suggest that selenium Se(IV) can prevent prostate cancer. Selol, a new organic semisynthetic derivative of Se(IV), is a mixture of selenitetriglycerides. This mixture is non-toxic and non-mutagenic, and after po treatment - 56-times less toxic (in mice) than sodium selenite. It exhibits strong anti-cancer activity in vitro in many cancer cell lines and can overcome the cell resistance to doxorubicin. Selol seems a promising compound for prostate cancer therapy.
The aim of the present study is the evaluation of Selol's influence on intracellular redox state (Eh) of prostatic tumors and the liver in androgen-dependent hPCa-bearing mice, and extracellular redox state in serum of these mice.
The anticancer activity of Selol involves perturbation of the redox regulation in the androgen dependent hPCa (LNCaP) cells, but not in healthy cells. After Selol treatment, intracellular Eh has increased in tumors from -223 mV to -175 mV, while in serum it has decreased (-82 mV vs -113 mV). It shows significant changes Eh in the extra- and intracellular environment. The difference decreases from 141 mV to 62 mV. The changes suggest that a tumor cell was probably directed toward apoptosis. This is exemplified in a significant decrease in cancer tumor mass by approx. 17% after the three weeks of Selol administration.
人类前列腺癌(hPCa)是老年男性中最常被诊断出的癌症,也是男性癌症死亡的第二大主要原因。来自流行病学、生态环境、营养预防和临床试验的数据表明,硒(IV)可以预防前列腺癌。硒醇(Selol)是硒(IV)的一种新型有机半合成衍生物,是亚硒酸甘油酯的混合物。这种混合物无毒且无致突变性,经口服给药后,其毒性(在小鼠中)比亚硒酸钠低56倍。它在许多癌细胞系中体外表现出强大的抗癌活性,并且可以克服细胞对阿霉素的耐药性。硒醇似乎是一种有前景的前列腺癌治疗化合物。
本研究的目的是评估硒醇对雄激素依赖性荷hPCa小鼠前列腺肿瘤和肝脏细胞内氧化还原状态(Eh)以及这些小鼠血清细胞外氧化还原状态的影响。
硒醇的抗癌活性涉及对雄激素依赖性hPCa(LNCaP)细胞中氧化还原调节的干扰,但对健康细胞无此作用。硒醇处理后,肿瘤细胞内Eh从-223 mV增加到-175 mV,而血清中Eh则降低(从-113 mV降至-82 mV)。这表明细胞内外环境中的Eh有显著变化。差异从141 mV降至62 mV。这些变化表明肿瘤细胞可能正趋向于凋亡。这在硒醇给药三周后癌肿瘤质量显著降低约17%中得到体现。