Isodeoxyelephantopin Promotes Cell Death in Triple‐Negative Breast Cancer by Blocking <scp>STAT3</scp> Phosphorylation and Enhancing the Effectiveness of Paclitaxel

Triple-negative breast cancer (TNBC) is an aggressive and challenging subtype of breast cancer, presenting patients with a more complex treatment journey. This underscores the critical need for ongoing research and the development of effective therapies to enhance patient outcomes. Signal transducer and activator of transcription 3 (STAT3) is a crucial transcription factor that regulates various cellular processes, including proliferation, survival, and immune modulation. Its constitutive activation is frequently observed in multiple cancer types, contributing to tumor progression and immune evasion. Isodeoxyelephantopin (IDET) is a bioactive compound extracted from the traditional medicinal plant <i>Elephantopus scaber</i>, yet its anti-tumor mechanisms require further investigation for a comprehensive understanding. The expression of indicated proteins was detected by Western blot analysis. Viability was evaluated using the trypan blue exclusion test. The combination index (CI) values were determined using CompuSyn software, based on the Chou-Talalay method. The anti-tumor activity of IDET combined with paclitaxel in vivo was confirmed in nude mice. In this study, we initially discovered that inhibiting STAT3 phosphorylation plays a vital role in the anti-tumor activity of IDET against TNBC. Furthermore, we found that IDET can enhance the anti-tumor activity of cisplatin and paclitaxel. Mechanistically, the inhibition of STAT3 phosphorylation is pivotal in mediating the synergistic anti-tumor effects observed with the combination of IDET and paclitaxel. Importantly, IDET also enhances the anti-tumor activity of paclitaxel in vivo. Taken together, our study reveals a novel mechanism of IDET and provides a potential strategy for treating TNBC.