Flörkemeier Inken, Steinhauer Tamara N, Hedemann Nina, Weimer Jörg Paul, Rogmans Christoph, van Mackelenbergh Marion T, Maass Nicolai, Clement Bernd, Bauerschlag Dirk O
Department of Gynaecology and Obstetrics, Christian-Albrechts-University Kiel and University Medical Center Schleswig-Holstein Campus Kiel, 24105 Kiel, Germany.
Pharmaceutical Institute, Department of Pharmaceutical and Medicinal Chemistry, Christian-Albrechts-University Kiel, 24118 Kiel, Germany.
Cancers (Basel). 2021 Dec 21;14(1):2. doi: 10.3390/cancers14010002.
Breast cancer constitutes the leading cause of cancer deaths among females. However, numerous shortcomings, including low bioavailability, resistance and significant side effects, are responsible for insufficient treatment. The ultimate goal, therefore, is to improve the success rates and, thus, the range available treatment options for breast cancer. Consequently, the identification, development and evaluation of potential novel drugs such as P8-D6 with seminal antitumor capacities have a high clinical need. P8-D6 effectively induces apoptosis by acting as a dual topoisomerase I/II inhibitor. This study provides an overview of the effectiveness of P8-D6 in breast cancer with both 2D monolayers and 3D spheroids compared to standard therapeutic agents. For this drug effectiveness review, cell lines and ex vivo primary cells were used and cytotoxicity, apoptosis rates and membrane integrity were examined. This study provides evidence for a significant P8-D6-induced increase in apoptosis and cytotoxicity in breast cancer cells compared to the efficacy of standard therapeutic drugs. To sum up, P8-D6 is a fast and powerful inductor of apoptosis and might become a new and suitable therapeutic option for breast cancer in the future.
乳腺癌是女性癌症死亡的主要原因。然而，包括生物利用度低、耐药性和显著副作用在内的诸多缺点导致治疗效果不佳。因此，最终目标是提高成功率，从而扩大乳腺癌的可用治疗方案范围。因此，鉴定、开发和评估具有开创性抗肿瘤能力的潜在新药（如P8-D6）具有很高的临床需求。P8-D6作为一种双重拓扑异构酶I/II抑制剂，可有效诱导细胞凋亡。本研究概述了与标准治疗药物相比，P8-D6在二维单层细胞和三维球体中对乳腺癌的有效性。在这项药物有效性评估中，使用了细胞系和离体原代细胞，并检测了细胞毒性、凋亡率和膜完整性。与标准治疗药物的疗效相比，本研究提供了证据，证明P8-D6可显著诱导乳腺癌细胞凋亡并增加细胞毒性。综上所述，P8-D6是一种快速且强大的细胞凋亡诱导剂，未来可能成为乳腺癌新的合适治疗选择。
