Abstract
Lectins are a unique class of carbohydrate binding proteins/glycoproteins, and many of them possess anticancer properties. They can induce cell cycle arrest and apoptosis, inhibit protein synthesis, telomerase activity and angiogenesis in cancer cells. In the present study, we have demonstrated the effect of Morus alba leaf lectin (MLL) on anoikis induction in MCF-7 cells. Anoikis induction in cancer cells has a significant role in preventing early stage metastasis. MLL treatment in monolayers of MCF-7 cells caused significant detachment of cells in a time and concentration dependent manner. The detached cells failed to re-adhere and grew even to culture plates coated with different matrix proteins. DNA fragmentation, membrane integrity studies, annexin V staining, caspase 9 activation and upregulation of Bax/Bad confirmed that the detached cells underwent apoptosis. Upregulation of matrix metalloproteinase 9 (MMP-9) caused a decrease in fibronectin (FN) production which facilitated the cells to detach by blocking the FN mediated downstream signaling. On treatment with MLL, we have observed downregulation of integrin expression, decreased phosphorylation of focal adhesion kinase (FAK), loss in FAK-integrin interaction and active Ras. MLL treatment downregulated the levels of phosphorylated Akt and PI3K. Also, we have studied the effect of MLL on two stress activated protein kinases p38 MAPK and JNK. p38 MAPK activation was found to be elevated, but there was no change in the level of JNK. Thus our study substantiated the possible antimetastatic effect of MLL by inducing anoikis in MCF-7 cells by activation of caspase 9 and proapoptotic Bax/Bad by blockage of FN mediated integrin/FAK signaling and partly by activation of p38 MAPK.
Highlights
Lectins are carbohydrate binding proteins/glycoproteins with diverse biological applications and are considered as one of the potent anticancer agents in future
We have demonstrated the effect of Morus alba leaf lectin (MLL) on anoikis induction in MCF-7 cells
In order to study the effect of Morus alba Leaf Lectin (MLL) on detachment induced cell death in MCF-7 cells, confluent monolayers of cells were treated with varying concentrations (2, 5, and 10 μg/ml) of MLL for different time intervals (4, 8, 12, 24, and 48 h) and observed for detachment of cells from the culture dishes
Summary
Lectins are carbohydrate binding proteins/glycoproteins with diverse biological applications and are considered as one of the potent anticancer agents in future. A heterodimeric glycoprotein isolated from Abrus precatorius mediated caspase induced cell death in vitro and in vivo in human liver cancer cells. It decreased Akt phosphorylation, HSP 90, CD 31 and Ki67 expression in HepG2 xenografted nude mice (Mukhopadhyay et al, 2014). Lectin from the fungus Sclerotium rolfsii exerted cytotoxic effects in human colon cancer cells by altering the expression of the genes involved in apoptosis, cell cycle regulation, MAPK and JNK signaling cascades (Barkeer et al, 2015). We have reported previously that an N-acetyl galactosamine lectin from Morus alba showed cell cycle arrest and caspase dependent apoptosis in human colon and breast cancer cells (Deepa and Priya, 2012; Deepa et al, 2012)
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