RESUMEN
Anaplastic thyroid cancer (ATC) is an aggressive form of thyroid cancer (TC), accounting for 50% of total TC-related deaths. Although therapeutic approaches against TC have improved in recent years, the survival rate remains low, and severe adverse effects are commonly reported. However, unexplored alternatives based on natural compounds, such as lysicamine, an alkaloid found in plants with established cytotoxicity against breast and liver cancers, offer promise. Therefore, this study aimed to explore the antineoplastic effects of lysicamine in papillary TC (BCPAP) and ATC (HTH83 and KTC-2) cells. Lysicamine treatment reduced cell viability, motility, colony formation, and AKT activation while increasing the percentage of necrotic cells. The absence of caspase activity confirmed apoptosis-independent cell death. Necrostatin-1 (NEC-1)-mediated necrosome inhibition reduced lysicamine-induced necrosis in KTC-2, suggesting necroptosis induction via a reactive oxygen species (ROS)-independent mechanism. Additionally, in silico analysis predicted lysicamine target proteins, particularly those related to MAPK and TGF-ß signaling. Our study demonstrated lysicamine's potential as an antineoplastic compound in ATC cells with a proposed mechanism related to inhibiting AKT activation and inducing cell death.
RESUMEN
OBJECTIVE: Breast cancer (BC) is the main cause of cancer-related deaths in women across the world. It can be classified into different subtypes, including triple-negative (TN), which is characterized by the absence of hormone receptors for estrogen and progesterone and the lack of the human epidermal growth factor receptor 2. These tumors have high heterogeneity, acquire therapeutic resistance, and have no established target-driven treatment yet. The identification of differentially expressed genes in TN breast tumors and the in silico validation of their prognostic role in these tumors. MATERIALS AND METHODS: We employed a microarray dataset and, by using the GEO2R tool, we identified a list of differentially expressed genes. The in silico validation was conducted using several online platforms including the KM Plotter, cBioPortal, bc-GenExMiner, Prognoscan, and Roc Plotter. RESULTS: We observed that FZD9 was among the top differentially expressed genes in a cohort of patients with different TNBC subtypes. The FZD9 expression was significantly different in TN breast tumors than in non-TN (nTN) breast tumors (p<0.0001), and the basal TN subtype showed the highest levels (p<0.0001). In addition, the FZD9 levels were significantly inversely and positively proportional (p<0.0001) to estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 clinical parameters. The high levels of FZD9 were associated with worse overall survival (p=0.007), relapse-free survival (p=5.8e-05), and worse survival in patients who received chemotherapy (p=3.2e-05; 0.007). CONCLUSION: Our cumulative results demonstrated that FZD9 plays an important role in TNBC and may be a potential prognostic biomarker. Nevertheless, further in vitro and in vivo assays are necessary to confirm our findings and to strengthen the evidences about the mechanisms by which FZD9 functions in these tumors.
