Kantapan Jiraporn, Innuan Phattarawadee, Kongkarnka Sarawut, Sangthong Padchanee, Dechsupa Nathupakorn
Molecular Imaging and Therapy Research Unit, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand.
Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand.
Pharmaceuticals (Basel). 2024 Dec 20;17(12):1729. doi: 10.3390/ph17121729.
Triple-negative breast cancer (TNBC) represents an aggressive form of breast cancer with few available therapeutic options. Chemotherapy, particularly with drugs like doxorubicin (DOX), remains the cornerstone of treatment for this challenging subtype. However, the clinical utility of DOX is hampered by adverse effects that escalate with higher doses and drug resistance, underscoring the need for alternative therapies. This study explored the efficacy of pentagalloyl glucose (PGG), a natural polyphenol derived from , in enhancing DOX's anticancer effects and suppressing the epithelial-mesenchymal transition (EMT) in TNBC cells. This study employed diverse methodologies to assess the effects of PGG and DOX on TNBC cells. MDA-MB231 triple-negative breast cancer cells were used to evaluate cell viability, migration, invasion, apoptosis, mitochondrial membrane potential, and protein expression through techniques including MTT assays, wound healing assays, flow cytometry, Western blotting, and immunofluorescence Our findings demonstrate that PGG combined with DOX significantly inhibits TNBC cell proliferation, migration, and invasion. PGG enhances DOX-induced apoptosis by disrupting the mitochondrial membrane potential and activating caspase pathways; consequently, the activation of caspase-3 and the cleavage of PARP are increased. Additionally, the study shows that the combination treatment upregulates ERK signaling, further promoting apoptosis. Moreover, PGG reverses DOX-induced EMT by downregulating mesenchymal markers (vimentin and β-catenin) and upregulating epithelial markers (E-cadherin). Furthermore, it effectively inhibits STAT3 phosphorylation, associated with cell survival and migration. These results highlight the potential of PGG as an adjuvant therapy in TNBC treatment. PGG synergizes with DOX, which potentiates its anticancer effects while mitigating adverse reactions.
三阴性乳腺癌（TNBC）是一种侵袭性乳腺癌，可用的治疗选择很少。化疗，尤其是使用阿霉素（DOX）等药物，仍然是这种具有挑战性的亚型治疗的基石。然而，DOX的临床应用受到不良反应的阻碍，这些不良反应会随着剂量的增加而加剧，并且会产生耐药性，这突出了对替代疗法的需求。本研究探讨了五倍子酰葡萄糖（PGG）（一种从[来源未提及]中提取的天然多酚）在增强DOX的抗癌作用和抑制TNBC细胞上皮-间质转化（EMT）方面的功效。本研究采用了多种方法来评估PGG和DOX对TNBC细胞的影响。使用MDA-MB231三阴性乳腺癌细胞，通过MTT法、伤口愈合试验、流式细胞术、蛋白质印迹法和免疫荧光等技术评估细胞活力、迁移、侵袭、凋亡、线粒体膜电位和蛋白质表达。我们的研究结果表明，PGG与DOX联合使用可显著抑制TNBC细胞的增殖、迁移和侵袭。PGG通过破坏线粒体膜电位和激活半胱天冬酶途径增强DOX诱导的凋亡；因此，半胱天冬酶-3的激活和PARP的裂解增加。此外，研究表明联合治疗上调ERK信号传导，进一步促进凋亡。此外，PGG通过下调间充质标志物（波形蛋白和β-连环蛋白）和上调上皮标志物（E-钙黏蛋白）来逆转DOX诱导的EMT。此外，它有效抑制与细胞存活和迁移相关的STAT3磷酸化。这些结果突出了PGG作为TNBC治疗辅助疗法的潜力。PGG与DOX协同作用，增强其抗癌作用，同时减轻不良反应。
