Triple negative breast cancer (TNBC) is an aggressive subtype characterized by the absence of estrogen and progesterone receptors, as well as HER2 overexpression. Due to the lack of specific targeted therapies, there is a clear imperative to explore new therapeutic strategies.
Norcantharidin (NCTD), a promising natural compound, has previously shown antitumor effects against lung and liver malignancies. However, its impact on TNBC remains unknown. Therefore, our work aimed to investigate the potential therapeutic implications of NCTD in TNBC.
Using human (HS578T, MDA-MB231) and murine (4T1) TNBC cell lines, we observed a significant antiproliferative effect of NCTD with IC50 values of 56 μM, 15 μM and 35 μM respectively, as determined by the MTS assay. Moreover, fluorescence microscopy (acridine orange/BrEt staining), flow cytometry (Annexin V/IP staining) and Western blot analysis (modulation of cleaved caspase 3, Parp and LC3-I/LC3II levels) revealed apoptosis and autophagy induction.
In vivo assays using BALB/c mice further supported our findings. Systemic administration of NCTD (2.5 and 3.75 mg/kg) significantly reduced both tumor size and local recurrence (p< 0.001 and p<0.01 respectively). This result is probably due not only to an effect on tumor mass, but also to an impact on cancer stem cells (CSC), since in vitro studies demonstrated that NCTD affects oncospheres formation ability.
In conclusion, our study highlights the significant antitumor activity of NCTD in TNBC, offering promising possibilities for its application as a therapeutic option. However, further research is necessary to optimize NCTD's efficacy, explore combination therapies, and fully elucidate the molecular mechanisms involved in its action.