SPAD-1, a serine proteinase associated disintegrin from Russell's viper venom disrupts adhesion of MCF7 human breast cancer cells.

Navodipa Bhattacharya, Nivedita Kolvekar, Sukanta Mondal, Angshuman Sarkar, Dibakar Chakrabarty

Toxicon : official journal of the International Society on Toxinology 2023 Jan 01

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Serine Proteinase Associated Disintegrin-1 (SPAD-1) is a low molecular mass (26 kDa) positively charged protein purified from Russell's viper venom (RVV) possessing cytotoxic activity on MCF7, human breast cancer cells. Primary sequence analysis of the protein confirms that it is a novel Snake Venom Serine Proteinase (SVSP) and a member of the trypsin family. SPAD-1 contains a conserved triad of Histidine (H), Aspartic acid(D) and Serine(S) residues at its active site for proteinase activity and also an adjacent histidine-glycine-aspartic acid (HGD) disintegrin-like motif. The serine proteinase and disintegrin parts are functionally active and independent. SPAD-1 showed proteolytic digestion of fibrinogen and fibronectin, but laminin digestion was below the detectable limit. Proteolytically inactivated SPAD-1 inhibited collagen and ADP-induced platelet aggregation. This study proposes considering Serine Proteinase Associated Disintegrin (SPAD) as a new group of snake venom proteins. Members of this group contain a serine proteinase catalytic triad and a disintegrin-like motif. SPAD-1 caused visible morphological changes in MCF7 cells, including a reduction of the cell-to-cell attachments, rounding of cell shape and death, in vitro. SPAD-1 also showed a dose-dependent significant decrease in the invasive potency of breast cancer cells. Confocal microscopic analysis revealed the breakage of nuclei of the SPAD-1-treated cells. SPAD-1 also increased cell detachment from the poly L-lysine-coated, laminin-coated and fibronectin-coated culture plate matrices, confirming the disintegrin activity. This study concludes that SPAD-1 may be a good candidate for anti-tumour drug design in the future. Copyright © 2022 Elsevier Ltd. All rights reserved.

Citation

Navodipa Bhattacharya, Nivedita Kolvekar, Sukanta Mondal, Angshuman Sarkar, Dibakar Chakrabarty. SPAD-1, a serine proteinase associated disintegrin from Russell's viper venom disrupts adhesion of MCF7 human breast cancer cells. Toxicon : official journal of the International Society on Toxinology. 2023 Jan 01;221:106979