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Cura, J.E., Blanzaco, D.P., Brisson, C., Cura, M.A., Cabrol, R., Larrateguy, L., Mendez, C., Sechi, J.C., Silveira, J.S., Theiller, E., de Roodt, A.R. and Vidal, J.C. (2002) Phase I and pharmacokinetics study of crotoxin (cytotoxic PLA2, NSC-624244) in patients with advanced cancer. Clinical Cancer Research, 8, 1033-1041.

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• TITLE: Patatin-like PLA2 with cytotoxicity against mammalian and plant tumour cells

  AUTHORS: Bernard Griffaut, Eric Debiton, Marie-Josèphe Galmier, Ana Mustel, Jean-Claude Madelmont, Gérard Ledoigt

  KEYWORDS: Cytotoxicity; Patatin; Phospholipase A2

  JOURNAL NAME: Advances in Biological Chemistry, Vol.3 No.5, October 24, 2013

  ABSTRACT: Plants can respond to traumatism by synthesis and secretion of defence molecules. Wound-healing and desiccation stress of pieces of potato tuber parenchyma (Solanum tuberosum) promoted the secretion of a patatin-like phospholipase A2, PLA2 (EC.3.1.1.4.) that displayed cytotoxic activity against tumour cells. The potato secretion product, an oligomeric form of patatin-like protein, was shown to contain several isoforms of PLA2 polypeptides and to be associated with other proteins, including Kunitz-type protease inhibitors. Patatin-like protein secretion was inhibited by vanadate. Secreted patatin-like proteins displayed specific features, such as extracellular function and low molecular weights, mainly 36 to 40 kDa. The 36-kDa polypeptide sequence was related to iPLA2α. Polypeptide spots of secreted patatin-like protein exhibited a nucleotide-binding consensus motif, GGGIKG that has been described in iPLA2 gene family. The cytotoxic agent caused cell death of plant crown-gall induced by Agrobacterium tumefaciens, and inhibited B16 cell proliferation, but at the same concentration did not display any toxicity against non-transformed cells. PLA2 enzyme activity was required for cytotoxicity against B16 melanoma cells. A model for such a specific activity against tumour cells is discussed in connection with asymmetric phospholipid patterns of cell membranes. In conclusion, secreted patatin-like PLA2 (e-patatin) may represent a novel therapeutic target for the development of new agents against cancer.