The effects of snake venoms as cytotoxins on selected prostate cancer cell lines

  • Basher M ABDALSAED

Student thesis: Doctoral Thesis

Abstract

Cancer is expected to claim 9 million deaths world-wide by the year 2020. Although there has been an increase in the sophistication of current therapeutic strategies, 40% of patients are still likely to die from the disease. Novel anticancer compounds are needed. Snake venoms may represent a relevant pool for selecting candidates that may have anticancer properties. Snake venoms are complex mixtures of unexplored sources of molecules with potential use in biomedical research and drug development. Some venom molecules are of low molecular weight and might trigger anticancer responses and could have potential therapeutic applications. In this study, selected snake venoms obtained from Naja pallida, Agkistrodon piscivorus conanti and Agkistrodon contortrix laticinctus were evaluated for cytotoxicity and selectivity in vitro against a panel of prostate cancer cell lines (DU145, PC3, LNCaP) and a non-malignant prostate epithelial cell line (PNT2A). The cytotoxicity activity of each venom was initially assessed using the SYTOX Green assay. SYTOX Green is a fluorescent nucleic acid indicator dye that can be used as a marker for cell death.The whole venoms, fractions and sub-fractions of Naja pallida, Agkistrodon piscivorus conanti and Agkistrodon contortrix laticinctus were tested and found to have activity ranging that from 0.1-20μg/ml against prostate cancer cell lines using an assay based on the release of lactate dehydrogenase (LDH). Further characterization of cytotoxic activity, and chemical analysis, including High Performance Liquid Chromatography (HPLC) guided fractionation, gel filtration and ion exchange chromatography has been conducted. The investigation of the possible mode of activity of the most cytotoxic venoms, and prospects for future work and on-going isolation and identification of pure anticancer compounds have been detailed in this study. The different fractions of low molecular weight (
Date of Award1 Aug 2013
LanguageEnglish
Awarding Institution
  • University Of Strathclyde
SupervisorEdward Rowan (Supervisor) & Alan Harvey (Supervisor)

Cite this