title: Synergistic effects of secretory phospholipase A2 from the venom of Agkistrodon piscivorus piscivorus with cancer chemotherapeutic agents.
abstract: Healthy cells typically resist hydrolysis catalyzed by snake venom secretory phospholipase A2. However, during various forms of programmed cell death, they become vulnerable to attack by the enzyme. This observation raises the question of whether the specificity of the enzyme for dying cells could be used as a strategy to eliminate tumor cells that have been intoxicated but not directly killed by chemotherapeutic agents. This idea was tested with S49 lymphoma cells and a broad range of antineoplastic drugs: methotrexate, daunorubicin, actinomycin D, and paclitaxel. In each case, a substantial population of treated cells was still alive yet vulnerable to attack by the enzyme. Induction of cell death by these agents also perturbed the biophysical properties of the membrane as detected by merocyanine 540 and trimethylammonium-diphenylhexatriene. These results suggest that exposure of lymphoma cells to these drugs universally causes changes to the cell membrane that render it susceptible to enzymatic attack. The data also argue that the snake venom enzyme is not only capable of clearing cell corpses but can aid in the demise of tumor cells that have initiated but not yet completed the death process.
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Nelson
authors.forename: Kristen
authors.initials: K
authors.lastname: Barlow
authors.forename: D Olin
authors.initials: DO
authors.lastname: Beck
authors.forename: Amanda
authors.initials: A
authors.lastname: Berbert
authors.forename: Nathan
authors.initials: N
authors.lastname: Eshenroder
authors.forename: Lyndee
authors.initials: L
authors.lastname: Francom
authors.forename: Mark
authors.initials: M
authors.lastname: Pruitt
authors.forename: Kina
authors.initials: K
authors.lastname: Thompson
authors.forename: Kyle
authors.initials: K
authors.lastname: Thompson
authors.forename: Brian
authors.initials: B
authors.lastname: Thurber
authors.forename: Celestine H-Y
authors.initials: CH
authors.lastname: Yeung
authors.forename: Allan M
authors.initials: AM
authors.lastname: Judd
authors.forename: John D
authors.initials: JD
authors.lastname: Bell
mesh_terms: D017836:Agkistrodon; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002462:Cell Membrane / Q000187:drug effects; D003435:Crotalid Venoms / Q000201:enzymology*; D006868:Hydrolysis; D008223:Lymphoma / Q000473:pathology; D051379:Mice; D009369:Neoplasms / Q000473:pathology*; D054497:Phospholipases A2, Secretory / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D003435:Crotalid Venoms; D054497:Phospholipases A2, Secretory