Department of Gerontology, Federal University of São Carlos, Rodovia Washington Luís, Km 235, CEP, São Carlos, SP, 13565-905, Brazil.
School of Pharmaceutical Sciences, São Paulo State University, Rodovia Araraquara - Jaú Km 1, CEP, Araraquara, SP, 14800-903, Brazil.
AAPS PharmSciTech. 2021 May 18;22(5):157. doi: 10.1208/s12249-021-02006-w.
The apoptotic, cytotoxic, and cytostatic activities for [10]-gingerol in triple-negative breast cancer cells (TNBCs) were already reported. However, despite these important antitumor activities, the compound has the disadvantage to have a hydrophobic characteristic, hindering in vivo administration. To surpass this issue, in this study we have created a [10]-gingerol-loaded nanoemulsion (10GNE) in order to increase the stability and solubility of the compound. The nanoemulsion was characterized and tested for its cytotoxic, cytostatic, and apoptotic effects on a panel of murine and human TNBC cell lines, as well as non-tumor cells, and compared with a [10]-gingerol-free nanoemulsion (NE) and with [10]-gingerol itself. Except for the murine 4T1.13 cell line, the IC of the free 10G molecule, after 72 h of incubation, was higher in all cell lines tested, both murine and human, demonstrating therefore the efficacy of the 10GNE regarding cytotoxicity. In murine tumor cells, 60 μM 10GNE was able to arrest cell cycle at sub-G0 phase and induce apoptosis, leading to 48% and 78% of total cell death in 4T1.13 and 4T1Br4 murine tumor cells, respectively. This represents an improvement compared to 10G-free molecule that only induced 74% of total apoptosis at 100 μM in 4T1Br4 cells. Taken together, our results show that nanoformulation preserved the [10]-gingerol cytotoxic and cytostatic properties and improved its apoptotic function on murine TNBC cell lines. These data open new perspectives to a more suitable drug-delivery approach for [10]-gingerol for TNBC treatment that should be further demonstrated using in vivo assays.
[10]-姜烯酚在三阴性乳腺癌细胞（TNBC）中的凋亡、细胞毒性和细胞抑制活性已经有报道。然而，尽管具有这些重要的抗肿瘤活性，但该化合物具有疏水性特征，这阻碍了其在体内的给药。为了克服这个问题，在这项研究中，我们制备了负载[10]-姜烯酚的纳米乳剂（10GNE），以提高化合物的稳定性和溶解度。我们对纳米乳剂进行了表征，并测试了其对一系列鼠源和人源 TNBC 细胞系以及非肿瘤细胞的细胞毒性、细胞抑制和凋亡作用，并与不含[10]-姜烯酚的纳米乳剂（NE）和[10]-姜烯酚本身进行了比较。除了鼠源 4T1.13 细胞系外，在所有测试的细胞系中，游离 10G 分子的 IC 在 72 小时孵育后均高于其他细胞系，这表明 10GNE 对细胞毒性有效。在鼠源肿瘤细胞中，60 μM 10GNE 能够使细胞周期在 sub-G0 期停滞，并诱导细胞凋亡，导致 4T1.13 和 4T1Br4 鼠源肿瘤细胞的总细胞死亡分别达到 48%和 78%。与游离 10G 分子在 4T1Br4 细胞中仅在 100 μM 时诱导 74%的总凋亡相比，这是一个改进。总的来说，我们的结果表明，纳米制剂保留了[10]-姜烯酚的细胞毒性和细胞抑制特性，并提高了其在鼠源 TNBC 细胞系中的凋亡功能。这些数据为 TNBC 治疗中[10]-姜烯酚更合适的药物输送方法开辟了新的前景，应该使用体内实验进一步证明。
