Silurus asotus egg lectin (SAL) is an α-galactoside-binding protein, isolated from the egg of catfish. It belongs to the rhamnose-binding lectin family that binds to Gb3 glycan (Galα1-4Galβ1-4Glc). SAL has resulted in the induction of early apoptosis in the Raji cell line, which is a Burkitt's lymphoma cell line expressing Gb3. The apoptosis was characterized by i) increased externalization of phosphatidylserin via multidrug resistance 1 P-glycoprotein (MDR1 P-gp), and ii) reduced cell size through the activation of voltage-gated potassium channel Kv1.3. Although the incorporation of propidium iodide (PI) was observed, SAL did not cause apoptosis in Raji cells. This event may be due to an increased expression of membrane-anchored tumor necrosis factor α (TNFα) and TNF receptor 1 (TNFR1) after the binding of SAL to Gb3. Moreover, SAL arrested the cell cycle at the G0/1 phase, thus inhibiting cell proliferation. The suppression of cell proliferation by SAL was likely due to the enhanced expression of p21 caused by the phosphorylation of ERK1/2 through the Ras-MEK-ERK1/2 pathway. Combination of SAL with anti-cancer drugs was also examined in this study. Interestingly, SAL increased the incorporation of doxorubicin (Dox) into Raji cells, consequently enhancing its cytotoxic effect. Similarly, the cytotoxic effects of vinblastine and irinotecan were also significantly increased in Raji cells treated with SAL. These studies demonstrate that SAL may be applied to cancer therapy.
Keywords: Silurus asotus egg lectin; anti-cancer drug; cell cycle arrest; globotriaosylceramide.