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[10]-姜辣素诱导三阴性乳腺癌细胞凋亡并抑制其转移扩散。

[10]-gingerol induces apoptosis and inhibits metastatic dissemination of triple negative breast cancer .

作者信息

Martin Ana Carolina B M, Fuzer Angelina M, Becceneri Amanda B, da Silva James Almada, Tomasin Rebeka, Denoyer Delphine, Kim Soo-Hyun, McIntyre Katherine A, Pearson Helen B, Yeo Belinda, Nagpal Aadya, Ling Xiawei, Selistre-de-Araújo Heloisa S, Vieira Paulo Cézar, Cominetti Marcia R, Pouliot Normand

机构信息

Department of Gerontology, Federal University of São Carlos, São Carlos, SP, Brazil.

Department of Chemistry, Federal University of São Carlos, São Carlos, SP, Brazil.

出版信息

Oncotarget. 2017 Aug 10;8(42):72260-72271. doi: 10.18632/oncotarget.20139. eCollection 2017 Sep 22.

Abstract

There is increasing interest in the use of non-toxic natural products for the treatment of various pathologies, including cancer. In particular, biologically active constituents of the ginger oleoresin ( Roscoe) have been shown to mediate anti-tumour activity and to contribute to the anti-inflammatory, antioxidant, antimicrobial, and antiemetic properties of ginger. Here we report on the inhibitory properties of [10]-gingerol against metastatic triple negative breast cancer (TNBC) and . We show that [10]-gingerol concentration-dependently induces apoptotic death in mouse and human TNBC cell lines . In addition, [10]-gingerol is well tolerated , induces a marked increase in caspase-3 activation and inhibits orthotopic tumour growth in a syngeneic mouse model of spontaneous breast cancer metastasis. Importantly, using both spontaneous and experimental metastasis assays, we show for the first time that [10]-gingerol significantly inhibits metastasis to multiple organs including lung, bone and brain. Remarkably, inhibition of brain metastasis was observed even when treatment was initiated after surgical removal of the primary tumour. Taken together, these results indicate that [10]-gingerol may be a safe and useful complementary therapy for the treatment of metastatic breast cancer and warrant further investigation of its efficacy, either alone or in combination with standard systemic therapies, in pre-clinical models of metastatic breast cancer and in patients.

摘要

人们对使用无毒天然产物治疗包括癌症在内的各种病症的兴趣与日俱增。特别是,姜油树脂(罗斯科)的生物活性成分已被证明具有介导抗肿瘤活性,并有助于姜的抗炎、抗氧化、抗菌和止吐特性。在此,我们报告[10]-姜酚对转移性三阴性乳腺癌(TNBC)的抑制特性。我们表明,[10]-姜酚在小鼠和人TNBC细胞系中浓度依赖性地诱导凋亡性死亡。此外,[10]-姜酚耐受性良好,可显著增加caspase-3的激活,并在自发性乳腺癌转移的同基因小鼠模型中抑制原位肿瘤生长。重要的是,使用自发性和实验性转移试验,我们首次表明[10]-姜酚可显著抑制向包括肺、骨和脑在内的多个器官的转移。值得注意的是,即使在手术切除原发性肿瘤后开始治疗,也观察到对脑转移的抑制作用。综上所述,这些结果表明,[10]-姜酚可能是一种安全有效的转移性乳腺癌辅助治疗方法,值得在转移性乳腺癌的临床前模型和患者中进一步研究其单独或与标准全身治疗联合使用的疗效。

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