Unit of Excellence on Research and Development of Cancer Therapy, University of Phayao, Phayao 56000, Thailand; Division of Biochemistry, School of Medical Sciences, University of Phayao, Phayao 56000, Thailand.
Siriraj Center of Research Excellence for Cancer Immunotherapy (SiCORE-CIT), Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
Biomed Pharmacother. 2023 Oct;166:115286. doi: 10.1016/j.biopha.2023.115286. Epub 2023 Aug 12.
Triple-negative breast cancer (TNBC) is a highly aggressive subtype currently lacking effective treatment options. Consequently, novel and effective drugs or compounds are urgently needed to treat TNBC. Therefore, this study aimed to evaluate the potential of 7R-acetylmelodorinol (7R-AMDL), a phytochemical compound isolated from Xylopia pierrei Hance, a plant found in Thailand, as a novel therapeutic agent for TNBC. MTT and clonogenic assays showed that 7R-AMDL significantly reduced the survival of breast cancer cell lines, with a markedly potent effect on MDA-MB-231 cells. Flow cytometry showed that treating MDA-MB-231 cells with 7R-AMDL at the concentration of dose 8 µM significantly increased early and late apoptosis after 24 and 48 h compared to the control group (p < 0.0001). The highest tested 7R-AMDL dose upregulated the death receptors and their ligands, with extrinsic and intrinsic apoptosis pathways significantly activated via the caspase cascade, compared to the untreated group (p < 0.05). In addition, immunoblots showed decreased BCL2-like 1 (BCL2L1/Bcl-xL) expression (p < 0.0001). Furthermore, wound healing and Transwell assays showed that at a non-cytotoxic dose (≤4 µM), 7R-AMDL significantly inhibited the MDA-MB-231 cell migration and invasion. This reduction in cell migration was associated with decreased matrix metallopeptidase 9 (MMP-9) expression (p < 0.01) and nuclear factor kappa B (NF-κB) activation (p < 0.05). Altogether, 7R-AMDL has anti-cancer effects against TNBC and the potential to be further developed and evaluated for treating this disease.
三阴性乳腺癌（TNBC）是一种高度侵袭性的亚型，目前缺乏有效的治疗选择。因此，迫切需要新型有效的药物或化合物来治疗 TNBC。因此，本研究旨在评估从泰国植物 Xylopia pierrei Hance 中分离得到的植物化学化合物 7R-乙酰梅尔多利诺林（7R-AMDL）作为治疗 TNBC 的新型治疗剂的潜力。MTT 和集落形成实验表明，7R-AMDL 显著降低乳腺癌细胞系的存活率，对 MDA-MB-231 细胞的作用尤为显著。流式细胞术显示，与对照组相比，用 7R-AMDL 处理 MDA-MB-231 细胞在 8μM 的浓度下，在 24 和 48 小时后，早期和晚期凋亡明显增加（p<0.0001）。与未经处理的组相比，最高测试剂量的 7R-AMDL 上调了死亡受体及其配体，通过 caspase 级联反应显著激活了外在和内在凋亡途径（p<0.05）。此外，免疫印迹显示 BCL2 样 1（BCL2L1/Bcl-xL）表达减少（p<0.0001）。此外，划痕愈合和 Transwell 实验表明，在非细胞毒性剂量（≤4μM）下，7R-AMDL 显著抑制 MDA-MB-231 细胞迁移和侵袭。细胞迁移减少与基质金属蛋白酶 9（MMP-9）表达减少（p<0.01）和核因子 kappa B（NF-κB）激活（p<0.05）有关。总之，7R-AMDL 对 TNBC 具有抗癌作用，并有可能进一步开发和评估用于治疗这种疾病。
