Department of Pharmacology, PSG College of Pharmacy, Coimbatore,India.
J Pharm Pharmacol. 2021 Apr 27;73(6):749-757. doi: 10.1093/jpp/rgab018.
Taxane based conventional chemotherapy serves as the standard treatment regimen for triple-negative breast cancer (TNBC). However, the efficacy is plateaued due to toxicities, chemoresistance and metastasis. Hence, the development of new therapies that provide long-term cover is needed. Brusatol, a natural quassinoid, has been implicated to inhibit the migration and proliferation of metastatic cells in lung and liver carcinoma, but its efficacy in TNBC has not been explored.
The growth inhibitory activity on TNBC cells was measured using MTT assay and flow cytometry. Epithelial to mesenchymal transition (EMT) and apoptotic markers were quantified using western blotting. The caspases using Calorimetric assay.
Brusatol along with paclitaxel showed an enhanced growth inhibitory activity and a combined synergistic effect. In addition, brusatol was also observed to inhibit the invasion, migratory potential of TNBC cells. Mechanistically, brusatol and its combination were observed to decrease the matrix metalloproteinase (MMP) and a modest increase in the reactive oxygen species (ROS) production. Furthermore, brusatol treatment activated both intrinsic and extrinsic pathways with morphological changes of apoptosis in TNBC cells.
This is the first in vitro report demonstrating antineoplastic, anti-EMT and synergistic activity of brusatol and in combination with paclitaxel in TNBC cell. Further in-vivo studies are needed to substantiate the above findings.
基于紫杉烷的常规化疗是三阴性乳腺癌（TNBC）的标准治疗方案。然而，由于毒性、化疗耐药性和转移，疗效趋于稳定。因此，需要开发提供长期覆盖的新疗法。布瑞沙托（Brusatol）是一种天然的苦木苦味素，已被证实可抑制肺癌和肝癌中转移性细胞的迁移和增殖，但它在 TNBC 中的疗效尚未得到探索。
使用 MTT 法和流式细胞术测量 TNBC 细胞的生长抑制活性。使用 Western blot 定量上皮间质转化（EMT）和凋亡标志物。使用比色法测定半胱天冬酶。
布瑞沙托与紫杉醇联合使用显示出增强的生长抑制活性和协同作用。此外，布瑞沙托还被观察到抑制 TNBC 细胞的侵袭和迁移能力。从机制上讲，布瑞沙托及其组合被观察到降低基质金属蛋白酶（MMP），同时适度增加活性氧（ROS）的产生。此外，布瑞沙托处理激活了内在和外在途径，并导致 TNBC 细胞发生凋亡的形态变化。
这是第一项证明布瑞沙托具有抗肿瘤、抗 EMT 作用，并与紫杉醇联合具有协同作用的体外报告。需要进一步的体内研究来证实上述发现。
