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茄科植物扁叶刺茄的精油在前列腺癌细胞中的分析:活性氧在促凋亡活性中的相关性

Fabiana imbricata Ruiz & Pav. (Solanaceae) essential oil analysis in prostate cancer cells: relevance of reactive oxygen species in proapoptotic activity.

作者信息

Madrid Alejandro, Avola Rosanna, Graziano Adriana C E, Cardile Venera, Russo Alessandra

机构信息

Laboratorio de Productos Naturales y Síntesis Orgánica (LPNSO), Facultad de Ciencias Naturales y Exactas, Universidad de Playa Ancha, Avda. Leopoldo Carvallo 270, Playa Ancha, Valparaíso, 2340000, Chile.

Department of Medicine and Surgery, University of Enna "Kore", 94100 Enna, Italy.

出版信息

J Ethnopharmacol. 2025 Aug 29;352:120162. doi: 10.1016/j.jep.2025.120162. Epub 2025 Jun 17.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Fabiana imbricata Ruiz & Pav. (Solanaceae) is a Patagonian plant widely used in traditional medicine, in particular as a diuretic, digestive and for genito-urinary system diseases. Essential oils are considered promising candidates for prostate cancer treatments. Prostate cancer is the second leading cause of death among men. Therefore, new therapeutic strategies of prevention are needed for this tumor.

AIM OF THE STUDY

The present research was designed to explore the chemical composition of essential oil from fresh leaves of F. imbricata plants collected in Valparaíso region, Chile, and its activity on human prostate cancer cell lines.

MATERIALS AND METHODS

Chemical characterization was performed by chromatographic techniques and the biological activity was evaluated in androgen-sensitive (LNCaP) and androgen-insensitive (DU-145) human prostate cancer cell lines. The cells were exposed to essential oil for 72 h and cell viability and cell membrane integrity were evaluated. Genomic DNA and caspase-3 activity was tested to confirm the cell death for apoptosis. Western blot analysis was employed to evaluate the expression of Bcl-2, Bax, cleaved caspase-3, cleaved caspase-9, SOD, Hsp70 and STAT-3 proteins. Assays to evaluate reactive oxygen species (ROS) and GSH levels were also performed.

RESULTS

The results showed the capacity of essential oil, for its active components (oxygenated sesquiterpenes, 77.54 %), to reduce cell viability in prostate cancer cells. At a concentration of 200 μg/mL, the cell viability in LNCaP and DU-145 cells, was 23 % and 26 %, respectively. On the contrary, it showed no significant effect on normal cells, also at this high concentration. In addition, it induced apoptosis cell death, involving the downregulation of Hsp70 and STAT-3 proteins, correlated, at least in part, to an increase of reactive oxygen species (ROS).

CONCLUSIONS

This in vitro experimental preclinical study, suggesting a potential application of F. imbricata essential oil in prostate cancer, could be considered as a start point to design further research in animal experimental models and on its active components.

摘要

民族药理学相关性

扁叶刺茄(茄科)是一种巴塔哥尼亚植物,在传统医学中广泛使用,特别是作为利尿剂、消化剂以及用于治疗泌尿生殖系统疾病。精油被认为是前列腺癌治疗的有前景的候选物。前列腺癌是男性中第二大主要死因。因此,需要针对这种肿瘤的新的预防治疗策略。

研究目的

本研究旨在探索从智利瓦尔帕莱索地区采集的扁叶刺茄新鲜叶片中提取的精油的化学成分及其对人前列腺癌细胞系的活性。

材料与方法

通过色谱技术进行化学表征,并在雄激素敏感(LNCaP)和雄激素不敏感(DU-145)人前列腺癌细胞系中评估生物活性。将细胞暴露于精油72小时,并评估细胞活力和细胞膜完整性。测试基因组DNA和半胱天冬酶-3活性以确认细胞凋亡死亡。采用蛋白质免疫印迹分析评估Bcl-2、Bax、裂解的半胱天冬酶-3、裂解的半胱天冬酶-9、超氧化物歧化酶、热休克蛋白70和信号转导与转录激活因子-3蛋白的表达。还进行了评估活性氧(ROS)和谷胱甘肽水平的测定。

结果

结果表明,精油因其活性成分(氧化倍半萜,77.54%)而具有降低前列腺癌细胞活力的能力。在200μg/mL的浓度下,LNCaP和DU-145细胞的细胞活力分别为23%和26%。相反,即使在这种高浓度下,它对正常细胞也没有显著影响。此外,它诱导细胞凋亡死亡,涉及热休克蛋白70和信号转导与转录激活因子-3蛋白的下调,这至少部分与活性氧(ROS)的增加相关。

结论

这项体外实验性临床前研究表明扁叶刺茄精油在前列腺癌中有潜在应用,可被视为设计动物实验模型及其活性成分进一步研究的起点。

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