Abstract
OBJECTIVE: The Na(+), K(+)-ATPase (NKA) is involved in many cellular functions, and changes in its activity and expression have been linked to various diseases, including cancer. This study aims to investigate the potential anti-tumor effect of tetrodotoxin (TTX), a potent sodium channel blocker extracted from the pufferfish Chelonodon patoca, on nude mice (Balb/c nu) induced with breast cancer (4T1) to determine whether it can affect the activity of the NKA. METHODS: TTX was extracted using 2% acetic acid-methanol (v/v). To determine the lethal concentration of TTX, three concentrations of the TTX extract (1.5, 2.0, and 3.0 mg/kg) were injected into transgenic mice that had already been induced by the 4T1 cell line and bearing tumors. After 7-8 weeks of monitoring tumor volume, the mice were killed, and a portion of the tumors was fixed in Bouin's fixative for immunohistological analysis, while the rest was frozen for biochemical analysis. RESULTS: Biometric analysis of Balb/c nu mice indicated a notable reduction in tumor volume progression in the group subjected to TTX extract compared to the control group. Furthermore, immunohistochemical and biochemical analysis demonstrated a decrease in the intensity and activity of NKA in the TTX extract group compared to the control group. CONCLUSION: Our results indicate that TTX extract may have anti-tumor effects by inhibiting NKA activity. Therefore, considering the presence of TTX in the pufferfish extract, TTX could be a promising therapeutic candidate for controlling metastatic breast tumor growth and metastasis through NKA inhibition.