Department of Molecular Medicine, University of Padova, Padova, Italy.
Hematology Oncology Division, Department of Women's and Children's Health, University of Padova, Padova, Italy.
Int J Cancer. 2021 Sep 1;149(5):1129-1136. doi: 10.1002/ijc.33686. Epub 2021 Jun 11.
Aloe-emodin (1,8-dihydroxy-3-[hydroxymethyl]-anthraquinone), AE, is one of the active constituents of a number of plant species used in traditional medicine. We have previously identified, for the first time, AE as a new antitumor agent and shown that its selective in vitro and in vivo killing of neuroblastoma cells was promoted by a cell-specific drug uptake process. However, the molecular mechanism underlying the cell entry of AE has remained elusive as yet. In this report, we show that AE enters tumor cells via two of the five somatostatin receptors: SSTR2 and SSTR5. This observation was suggested by gene silencing, receptor competition, imaging and molecular modeling experiments. Furthermore, SSTR2 was expressed in all surgical neuroblastoma specimens we analyzed by immunohistochemistry. The above findings have strong implications for the clinical adoption of this natural anthraquinone molecule as an antitumor agent.
大黄素（1,8-二羟基-3-[羟甲基]-蒽醌），AE，是一种在传统医学中使用的多种植物物种的活性成分。我们以前首次将 AE 鉴定为一种新的抗肿瘤剂，并表明其对神经母细胞瘤细胞的选择性体外和体内杀伤作用是由细胞特异性药物摄取过程促进的。然而，AE 进入细胞的分子机制迄今仍未被发现。在本报告中，我们表明 AE 通过两种生长抑素受体（SSTR2 和 SSTR5）进入肿瘤细胞。这一观察结果是通过基因沉默、受体竞争、成像和分子建模实验得出的。此外，我们通过免疫组织化学分析了所有手术神经母细胞瘤标本，发现 SSTR2 均有表达。上述发现对将这种天然蒽醌分子作为抗肿瘤剂在临床上的应用具有重要意义。
