Sabeel Zufa, Chai Guangshuai, Chen Ruolan, Ying Lu, Liu Yan, Zhang Wenjing, Pan Shangyang, Chen Xiaoyang, Yu Changyuan, Yang Zhao
State Key Laboratory of Green Biomanufacturing, College of Life Science and Technology, Innovation Center of Molecular Diagnostics, Beijing University of Chemical Technology, Beijing 100029, China.
Int J Mol Sci. 2025 Jun 7;26(12):5469. doi: 10.3390/ijms26125469.
Breast cancer (BC) remains a significant therapeutic challenge, necessitating novel agents with multi-target efficacy. Here, we demonstrate that triptophenolide (TRI), a bioactive compound from Tripterygium wilfordii, exerts potent anti-BC activity across hormone-responsive (MCF-7) and triple-negative (MDA-MB-231) subtypes. In vitro, TRI inhibited proliferation in a concentration-dependent manner, with IC values decreasing from 180.3 μg/mL (24 h) to 127.2 μg/mL (48 h) in MCF-7 cells, and from 322.5 μg/mL to 262.1 μg/mL in MDA-MB-231 cells. TRI treatment induced G1-phase arrest in both breast cancer subtypes, increasing the G1 population by 22.27% in MCF-7 cells and 10.64% in MDA-MB-231 cells. Concurrently, TRI triggered apoptosis, elevating apoptotic rates from 3.36% to 9.78% in MCF-7 cells and from 7.01% to 17.02% in MDA-MB-231 cells. These effects were associated with the significant upregulation of pro-apoptotic proteins BAX, BAK1, BIM, and cytochrome c (CYCS). Notably, TRI suppressed migration by 61.5% (MCF-7) and 71.5% (MDA-MB-231). In vivo, TRI treatment inhibited MCF-7 xenograft growth and reduced tumor volume (1207.5 vs. 285 mm) and weight (0.22 vs. 0.1 g), while extending the survival time of tumor-bearing mice from 14-20 days to 24 days. These results position TRI as a promising lead therapeutic candidate against diverse BC subtypes, with mechanistic versatility surpassing single-target agents.
乳腺癌（BC）仍然是一个重大的治疗挑战，需要具有多靶点疗效的新型药物。在此，我们证明雷公藤甲素（TRI），一种来自雷公藤的生物活性化合物，对激素反应型（MCF-7）和三阴性（MDA-MB-231）亚型的乳腺癌均具有强大的抗乳腺癌活性。在体外，TRI以浓度依赖性方式抑制增殖，在MCF-7细胞中，IC值从180.3μg/mL（24小时）降至127.2μg/mL（48小时），在MDA-MB-231细胞中从322.5μg/mL降至262.1μg/mL。TRI处理在两种乳腺癌亚型中均诱导G1期阻滞，使MCF-7细胞中的G1期细胞群体增加22.27%，MDA-MB-231细胞中增加10.64%。同时，TRI触发细胞凋亡，使MCF-7细胞中的凋亡率从3.36%提高到9.78%，MDA-MB-231细胞中从7.01%提高到17.02%。这些效应与促凋亡蛋白BAX、BAK1、BIM和细胞色素c（CYCS）的显著上调有关。值得注意的是，TRI抑制迁移的比例分别为61.5%（MCF-7）和71.5%（MDA-MB-231）。在体内，TRI处理抑制了MCF-7异种移植瘤的生长，减小了肿瘤体积（1207.5对285mm）和重量（0.22对0.1g），同时将荷瘤小鼠的生存时间从14 - 20天延长至24天。这些结果表明TRI是一种针对多种乳腺癌亚型的有前景的先导治疗候选药物，其作用机制的多样性超过单靶点药物。
