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单萜烯 α-侧柏酮(柏木精油的主要化合物)治疗复发性恶性多形性胶质母细胞瘤的体外研究。

Therapeutic potential of monoterpene α-thujone, the main compound of Thuja occidentalis L. essential oil, against malignant glioblastoma multiforme cells in vitro.

机构信息

Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Kraków, Poland.

Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Kraków, Poland.

出版信息

Fitoterapia. 2019 Apr;134:172-181. doi: 10.1016/j.fitote.2019.02.020. Epub 2019 Feb 27.

Abstract

Thuja occidentalis L. is indigenous for Northern America and commonly cultivated in Europe. Raw materials obtained from this tree are widely applied in the ethnomedicine and phytotherapy of numerous ailments, incl. scurvy, cystitis, rheumatism and cancer. Despite wide medicinal applications of Thuja occidentalis, still little is known on its therapeutic potential in tumor treatment. α-thujone is the main component of Thuja occidentalis essential oil, which has been suggested to possess anti-tumor activities. This monoterpene easily penetrates the blood-brain barrier. Therefore, we examined its effects on the malignancy of glioblastoma multiforme (GBM) cells, with the special emphasis on the mechanisms of its effect on cell viability and invasiveness. α-thujone exerted the attenuating effect on the viability and proliferation of GBM cells when administered at the concentrations between 100 and 500 μg/ml (660 μM - 3.2 mM). This effect was correlated with the induction of apoptosis in GBM cell populations and with considerable inhibition of GBM cells motility. Mechanistic analyses demonstrated the induction of oxidative stress and autophagy in α-thujone-treated tumor cells, whereas normal astrocytes displayed considerably lower sensitivity to α-thujone. Our observations demonstrate that α-thujone exerts pro-apoptotic and anti-invasive effects on GBM cells. They confirm the potential of α-thujone for the treatment of glioblastoma multiforme.

摘要

西洋杉 Thuja occidentalis L. 原产于北美洲,在欧洲广泛种植。从这种树中提取的原料广泛应用于多种疾病的民族医学和植物疗法,包括坏血病、膀胱炎、风湿病和癌症。尽管西洋杉的药用应用广泛,但对于其在肿瘤治疗中的治疗潜力仍知之甚少。α-侧柏酮是西洋杉精油的主要成分,已被证明具有抗肿瘤活性。这种单萜类化合物很容易穿透血脑屏障。因此,我们研究了它对多形性胶质母细胞瘤(GBM)细胞恶性程度的影响,特别强调了它对细胞活力和侵袭性影响的机制。当以 100 至 500μg/ml(660μM-3.2mM)的浓度给药时,α-侧柏酮对 GBM 细胞的活力和增殖表现出减弱作用。这种作用与 GBM 细胞群体中细胞凋亡的诱导以及对 GBM 细胞运动性的相当大的抑制有关。机制分析表明,α-侧柏酮诱导肿瘤细胞发生氧化应激和自噬,而正常星形胶质细胞对 α-侧柏酮的敏感性较低。我们的观察结果表明,α-侧柏酮对 GBM 细胞具有促凋亡和抗侵袭作用。它们证实了 α-侧柏酮治疗多形性胶质母细胞瘤的潜力。

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