High Antitumor Activity of the Dual Topoisomerase Inhibitor P8-D6 in Breast Cancer

双拓扑异构酶抑制剂 P8-D6 在乳腺癌中具有较高的抗肿瘤活性

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作者:Inken Flörkemeier, Tamara N Steinhauer, Nina Hedemann, Jörg Paul Weimer, Christoph Rogmans, Marion T van Mackelenbergh, Nicolai Maass, Bernd Clement, Dirk O Bauerschlag

Abstract

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.

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