Rhizoctonia Bataticola Lectin (RBL) Induces Caspase-8-Mediated Apoptosis in Human T-Cell Leukemia Cell Lines but Not in Normal CD3 and CD34 Positive Cells

Abstract

We have previously demonstrated immunostimulatory activity of a fungal lectin, Rhizoctonia bataticola lectin (RBL), towards normal human peripheral blood mononuclear cells. The present study aimed to explore the anticancer activities of RBL using human leukemic T-cell lines, Molt-4, Jurkat and HuT-78. RBL exhibited significant binding (>90%) to the cell membrane that was effectively inhibited by complex glycoproteins such as mucin (97% inhibition) and asialofetuin (94% inhibition) but not simple sugars such as N-acetyl-D-galactosamine, glucose and sucrose. RBL induced a dose and time dependent inhibition of proliferation and induced cytotoxicity in the cell lines. The percentage of apoptotic cells, as determined by hypodiploidy, was 33% and 42% in Molt-4 and Jurkat cells, respectively, compared to 3.11% and 2.92% in controls. This effect was associated with a concomitant decrease in the G0/G1 population. Though initiator caspase-8 and -9 were activated upon exposure to RBL, inhibition of caspase-8 but not caspase-9 rescued cells from RBL-induced apoptosis. Mechanistic studies revealed that RBL induced cleavage of Bid, loss of mitochondrial membrane potential and activation of caspase-3. The expression of the anti-apoptotic proteins Bcl-2 and Bcl-X was down regulated without altering the expression of pro-apoptotic proteins- Bad and Bax. In contrast to leukemic cells, RBL did not induce apoptosis in normal PBMC, isolated CD3+ve cells and undifferentiated CD34+ve hematopoietic stem and progenitor cells (HSPCs). The findings highlight the differential effects of RBL on transformed and normal hematopoietic cells and suggest that RBL may be explored for therapeutic applications in leukemia.

ArtinM Mediates Murine T Cell Activation and Induces Cell Death in Jurkat Human Leukemic T Cells

“…The glycocalyx O -glycans and/or N -glycans regulate the death of Jurkat T cells induced by lectins having distinct glycan-binding specificities, which can trigger apoptosis via caspase-dependent and/or -independent pathways [ 50 , 77 , 78 , 79 , 80 , 81 , 82 , 83 ]. We verified that ArtinM promotes the apoptosis of Jurkat T cells, as demonstrated by Annexin V staining and altered cell cycle progression.…”

“…Cell pellets were obtained by centrifugation at 300× g for 7 min at 4 °C. The cell concentration was maintained as recommended by the ATCC cell biology collection, a protocol that was successful adopted by several authors [ 50 , 77 , 80 , 82 ].…”

A mitogenic lectin from Rhizoctonia bataticola arrests growth, inhibits metastasis, and induces apoptosis in human colon epithelial cancer cells

“…In contrast, RBL has mitogenic response on normal human PBMCs revealing its clinical potential. 14,15 Exquisite specificity of RBL for high mannose N glycans, which are known to be abundantly expressed in human colon cancer cells, prompted the present study to evaluate its diagnostic and therapeutic potential in colon cancer. RBL which shows differential binding to primary and metastatic human colon cancer tissues compared to normal tissues indicates that RBL has the ability to recognize and bind to tumor specific glycans selectively expressed on human colon cancer tissues and hence has promising potential as diagnostic tool.…”

Fungal proteinaceous compounds with multiple biological activities

“…It downregulated the expression of anti-apoptotic Bcl-X and Bcl-2 but did not affect expression of pro-apoptotic Bax and Bad. It did not manifest apoptotic activity toward undifferentiated CD34+ve hematopoietic stem and progenitor cells, isolated CD3+ve cells, or normal human peripheral blood mononuclear cells (Pujari et al 2013). An 18-kDa lectin isolated from the mushroom Ganoderma capense (Lloyd) Teng exhibited antiproliferative activity toward leukemia (L1210 and M1) cells and hepatoma Hep G2 cells (Ngai and Ng 2004b).…”