Plant lectins have come into focus as potential therapeutic molecules by virtue of their potential for selective targeting of cancer cells. Hematological cancers are a worldwide health issue. Our study investigated the effects of Phaseolus vulgaris lectin (PHA), Phytolacca americana lectin (PAA), and Concanavalin A (ConA) on the acute monocytic leukemia cell line (THP-1). A range of lectin concentrations (0.39-200 µg/mL) was applied to THP-1 cells for different time intervals (24, 48, and 72 hr). MTT(3-(4,5-di methyl thiazol-2-yl)-2,5-diphenyltetrazolium bromide) test was performed to assess cell viability. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied for the evaluation of CASP3 (apoptosis), LC3 (autophagy), and AKT1 (cell survival). ConA and PHA exhibited mitogenic properties, with cell viabilities exceeding 100% reflecting immunostimulatory rather than cytotoxic effects. On the other hand, PAA showed strong cytotoxicity, lowering viability with maximum cytotoxicity up to 43-59% after 72 hr. Compared with untreated cells, PAA treatment induced CASP3 upregulation (28.7-57.9-fold), coinciding with LC3 activation (15.7-21.8-fold) and an unchanged level of AKT1, indicating simultaneous activation of apoptotic and autophagic pathways. In conclusion, PAA lectin exhibits superior anti-cancer activity by dual-activation of the death pathway of programmed cells, of which apoptosis is predominant. These results confirm PAA as a highly promising lead compound for further developing drugs against hematological cancers.