Phaseolus acutifolius Recombinant Lectin Exerts Differential Proapoptotic Activity on EGFR+ and EGFR− Colon Cancer Cells and Provokes T Cell-Assisted Antitumor Responses in Mice

<b>Background:</b><i>r</i>TBL-1, a recombinant lectin from <i>Phaseolus acutifolius</i>, exhibit proapoptotic activity on colon cancer cells and inhibitory properties on colon tumorigenesis in vivo. Apoptosis has been associated with a phospho-EGFR/phospho-p38/phospho-p53 mechanistic axis. Immunogenicity data have been observed in treated animals, but its possible involvement in the antitumor response remained unexplored. <b>Objective:</b> We investigated whether the cytotoxic activity of <i>r</i>TBL-1 depends on EGFR and its capacity to produce antitumor responses on syngeneic colon cancer in mice, with and without T cells, in order to explore its possible involvement in the process. <b>Results:</b><i>r</i>TBL-1 exhibited cytotoxic effects in a concentration-dependent manner in both EGFR⁺ (MC-38) and EGFR^- (CT-26) colon cancer cells with LC₅₀ values of 23.50 and 30.01 µg/mL, respectively (<i>p</i> = 0.063). Apoptotic effects were slower and longer-lasting in MC-38 than in CT-26 cells. Significant increases in caspase-3 proteolytic activation and PARP1 cleavage were detected in both cell types, despite PARP1 rheostasis in CT-26 cells. Intralesional treatment with <i>r</i>TBL-1 inhibited the growth of established tumors in immunocompetent BALB/c mice in 27.81% (<i>p</i> = 0.0008) with a benefit in survival (<i>p</i> = 0.022), but not in immunodeficient BALB/c nude mice. <b>Conclusions:</b><i>r</i>TBL-1 induces apoptosis in colon cancer cells by EGFR independent mechanisms, although its presence could be related to deeper responses. Unresponsiveness in nude mice indicated that <i>r</i>TBL-1 antitumor effect is the synergistic result of apoptosis induction and T cell-mediated cytotoxicity in the tumor. Future studies will focus on the immunogenic effects triggered by the antitumor activity of <i>r</i>TBL-1 in colon cancer.