Inhibition of Steroidogenesis in Prostate Cancer Cells by Both a Natural and Another Synthetic Steroid

IF 3.5 4区 医学 Q2 CHEMISTRY, MEDICINAL
Marisa Cabeza, Karla Mejía, Fernando García, Ivonne Heuze, Miguel Morales, Mauricio Rodríguez-Dorantes
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Abstract

Studies suggest that vegetarians and Asians have lower mortality rates from prostate cancer compared to men who follow a Western diet. β-sitosterol, a key compound of plant-based diets, has been found to induce significant changes in the ultrasonic structure of the prostatic adenomas, making it a promising candidate for further prostate cancer research. Consequently, we investigated the potential of β-sitosterol and the synthetic derivative 2 as potent inhibitors of androgen synthesis, a critical process for the growth and survival of prostate tumor LNCaP cells. Solubilized LNCaP microsomes were used as a source of SRD5A1 and AKR1C3 to monitor androgen synthesis from labeled androstenedione, both in the presence and absence of β-sitosterol or 2. Furthermore, the effect of these steroids on LNCaP viability was determined using the MTT method. Our findings revealed significant insights into the androgen synthesis pathways in LNCaP cells. The most efficient metabolic route for dihydrotestosterone formation was the conversion of androstenedione to 5α-androstanedione rather than from testosterone in LNCaP. This conclusion is supported by the Vmax values for 5α-androstanedione formation (271.05 ± 5.0 ng/mg protein/min) and the Vmax of testosterone formation (80.1 ± 8.0 ng/mg protein/min). Both β-sitosterol and 2 demonstrated substantial inhibitory effects of these enzymes for dihydrotestosterone formation and significantly reduced cell viability, highlighting their therapeutic potential. These findings enhance our understanding of the inhibitory effects of β-sitosterol and 2 on LNCaP cells and suggest their promising application in the treatment of prostate cancer.

Abstract Image

一种天然和另一种合成类固醇对前列腺癌细胞类固醇生成的抑制作用
研究表明,与遵循西方饮食的男性相比,素食者和亚洲人患前列腺癌的死亡率较低。β-谷甾醇是植物性饮食中的一种关键化合物,已被发现可诱导前列腺腺瘤的超声结构发生显著变化,使其成为进一步研究前列腺癌的有希望的候选物。因此,我们研究了β-谷甾醇及其合成衍生物2作为雄激素合成抑制剂的潜力,雄激素合成是前列腺肿瘤LNCaP细胞生长和存活的关键过程。溶解的LNCaP微粒体被用作SRD5A1和AKR1C3的来源,以监测标记雄烯二酮在存在和不存在β-谷甾醇或2的情况下的雄激素合成。此外,使用MTT法确定这些类固醇对LNCaP活力的影响。我们的发现揭示了LNCaP细胞中雄激素合成途径的重要见解。在LNCaP中,雄烯二酮转化为5α-雄烯二酮的代谢途径比从睾酮转化为雄烯二酮的代谢途径更有效。5α-雄甾二酮生成的Vmax值(271.05±5.0 ng/mg蛋白/min)和睾酮生成的Vmax值(80.1±8.0 ng/mg蛋白/min)支持了这一结论。β-谷甾醇和2均显示出这些酶对双氢睾酮形成的显著抑制作用,并显著降低细胞活力,突出了它们的治疗潜力。这些发现增强了我们对β-谷甾醇和β-谷甾醇2对LNCaP细胞抑制作用的认识,并提示其在前列腺癌治疗中的应用前景。
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来源期刊
CiteScore
6.40
自引率
2.60%
发文量
104
审稿时长
6-12 weeks
期刊介绍: Drug Development Research focuses on research topics related to the discovery and development of new therapeutic entities. The journal publishes original research articles on medicinal chemistry, pharmacology, biotechnology and biopharmaceuticals, toxicology, and drug delivery, formulation, and pharmacokinetics. The journal welcomes manuscripts on new compounds and technologies in all areas focused on human therapeutics, as well as global management, health care policy, and regulatory issues involving the drug discovery and development process. In addition to full-length articles, Drug Development Research publishes Brief Reports on important and timely new research findings, as well as in-depth review articles. The journal also features periodic special thematic issues devoted to specific compound classes, new technologies, and broad aspects of drug discovery and development.
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