title: Scorpion venom (Odontobuthus doriae) induces apoptosis by depolarization of mitochondria and reduces S-phase population in human breast cancer cells (MCF-7).
abstract: Venom of some species of scorpions induces apoptosis and arrests proliferation in cancer cells. This is an important property that can be harnessed and can lead to isolation of compounds of therapeutic importance in cancer research. Cytotoxicity was investigated using MTT reduction and confirmed with lactate dehydrogenase release following venom exposure. Apoptosis was evaluated with determination of mitochondrial membrane potential, reactive nitrogen species assay, measurement of Caspase-3 activity and DNA fragmentation analysis. To confirm that venom can inhibit DNA synthesis in proliferating breast cancer cells, immunocytochemical detection of BrdU incorporation was done. Our results demonstrated that venom of Odontobuthus doriae not only induced apoptosis but lead to the inhibition of DNA synthesis in human breast cancer cells (MCF-7). Cell viability decreased with parallel increment of LDH release in dose dependent manner after treatment with varying concentrations of venom. Moreover, venom depleted cellular antioxidants evidenced by depression of GSH and Catalases and concomitantly increased reactive nitrogen intermediates (RNI). These events were related to the depolarization of mitochondria and associated Caspase-3 activation following venom treatment in a concentration dependent manner. Finally, fragmentation of nuclear DNA following venom treatment confirmed the apoptotic property of the said venom. These results suggest that venom of O. doriae can be potential source for the isolation of effective anti-proliferative and apoptotic molecules.
authors.affiliation: Clinical Toxicology Laboratory, Department of Medical Elementology and Toxicology, Jamia Hamdard, Hamdard University, New Delhi 110 062, India.
authors.forename: Jamil
authors.initials: J
authors.lastname: Zargan
authors.forename: Sadiq
authors.initials: S
authors.lastname: Umar
authors.forename: Mir
authors.initials: M
authors.lastname: Sajad
authors.forename: M
authors.initials: M
authors.lastname: Naime
authors.forename: Shakir
authors.initials: S
authors.lastname: Ali
authors.forename: Haider A
authors.initials: HA
authors.lastname: Khan
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D053148:Caspase 3 / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D026361:Reactive Nitrogen Species / Q000378:metabolism; D016196:S Phase / Q000187:drug effects*; D012604:Scorpion Venoms / Q000494:pharmacology*
chemical_list: D026361:Reactive Nitrogen Species; D012604:Scorpion Venoms; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D053148:Caspase 3; D005978:Glutathione