新型百里醌衍生物TQFL28在体内外均能抑制三阴性乳腺癌（TNBC）的侵袭性。

Novel Thymoquinone Derivative TQFL28 Inhibits Triple-Negative Breast Cancer (TNBC) Invasiveness In Vitro and In Vivo.

作者信息

He Jiayue, Zou Hui, Wei Chunli, Du Jun, Xiao Ting, Li Ting, El-Far Ali, Cheng Jingliang, Fu Junjiang, Liu Xiaoyan

机构信息

Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou 646000, China.

Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, School of Medicine, Hunan Normal University, Changsha 410013, China.

出版信息

Curr Issues Mol Biol. 2025 Jun 1;47(6):412. doi: 10.3390/cimb47060412.

DOI:10.3390/cimb47060412

PMID:40699811

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12191647/

Abstract

Although thymoquinone (TQ) has been reported as an anti-tumor small molecule well investigated in numerous tumors. In this study, we designed and synthesized a novel TQ derivative, TQFL28, with a molecular formula of CHNO. TQFL28 showed stronger cytotoxicity or anti-proliferative activities against triple-negative breast cancer (TNBC) cell lines (BT549, MDA-MB-231, or 4T1) than TQ but is lower in the normal mammary epithelial cells, MCF10A. TQFL28 exhibited lower IC values toward BT549 (38.78 ± 1.589) and MDA-MB-231 (39.63 ± 1.598) cells compared to TQ, indicating its efficacy for TNBC cytotoxicity. TQFL28 inhibited the growth, migration, and invasiveness of TNBC cells of 4T1 and BT549 in vitro and tumor progression and metastasis in a 4T1 allograft animal model in vivo. Moreover, TQFL28 presents lower toxicity than TQ in mice, showing a 7-day half-lethal dose (LD) of 59.43 mg/kg (41.6-83.6, 95% confidence interval). Altogether, our study obtained. In addition, TQFL28 induced a significant reduction in tumor volumes in the mouse model in comparison to the vehicle group. TQFL28, a novel small molecule, has a superior inhibitory effect and lower toxicity on TNBC both in vitro and in vivo. Thus, TQFL28 might have potential as a therapeutic small molecule for breast cancer, especially in TNBC.

摘要

尽管百里醌（TQ）已被报道为一种在众多肿瘤中得到充分研究的抗肿瘤小分子。在本研究中，我们设计并合成了一种新型的TQ衍生物TQFL28，其分子式为CHNO。TQFL28对三阴性乳腺癌（TNBC）细胞系（BT549、MDA - MB - 231或4T1）显示出比TQ更强的细胞毒性或抗增殖活性，但在正常乳腺上皮细胞MCF10A中活性较低。与TQ相比，TQFL28对BT549（38.78±1.589）和MDA - MB - 231（39.63±1.598）细胞的IC值更低，表明其对TNBC细胞毒性的有效性。TQFL28在体外抑制4T1和BT549的TNBC细胞的生长、迁移和侵袭，并在体内的4T1同种异体移植动物模型中抑制肿瘤进展和转移。此外，TQFL28在小鼠中的毒性低于TQ，其7天半数致死剂量（LD）为59.43 mg/kg（41.6 - 83.6，95%置信区间）。总之，我们的研究表明。此外，与载体组相比，TQFL28在小鼠模型中使肿瘤体积显著减小。TQFL28作为一种新型小分子，在体外和体内对TNBC均具有优异的抑制作用和较低的毒性。因此，TQFL28可能有潜力作为一种治疗乳腺癌的小分子药物，尤其是在TNBC中。