Introduction:
Breast cancer constitutes the leading cause of cancer death among females1;2. Insufficient treatment options are responsible for cancer deaths. Although options have improved, breast cancer is still not sufficiently treatable due to chemotherapy resistance and treatment limitations by side effects. Hence, research on new drugs such as P8-D6 with promising antitumor properties is essential. P8-D6 is an effective inductor of apoptosis by acting as a dual topoisomerase inhibitor. Its outstanding proliferation inhibition was shown in NCI-60-DTP-human-tumor-cell-line-screening (GI50/60value: 49nM) and in further in vitro testings3,4.
Methods:
Viability and apoptosis of breast cancer cell lines and ex vivo primary cells after treatment with P8-D6 were determined by using ApoLive-Glo™ Multiplex Assay. For better comparison, cells were treated with different concentrations of P8-D6 and standard therapeutics for 48h. Likewise, the effects on non-cancer cells were analysed and hepatotoxicity of P8-D6 was investigated. The expression levels of topo I/II were measured by western blot. Fluorescence microscopy showed whether P8-D6 gets into the nucleus to its target.
Results:
The results indicate a significantly increase of apoptosis in cancer cells by P8-D6 than its references. Non-cancer cells were slightly effected. No hepatotoxic effect in in vitro studies was seen compared to PBS. By staining, P8-D6 was detected in the nuclei.
Conclusions:
P8-D6 has promising antitumor properties in in vitro studies on breast cancer. It has fewer side effects on normal cells than references and no hepatotoxic effect. Furthermore P8-D6 should be tested in 3D culture. P8-D6 is a strong and rapid inductor of apoptosis.
