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Orsolic, Nada
Arhiv za higijenu rada i toksikologiju, 09/2009, Letnik: 60, Številka: 3Journal Article
This study investigated possible growth-inhibiting effects of bee venom applied alone or in combination with a cytotoxic drug bleomycin on HeLa and V79 cells in vitro based on clone formation, cell counting, and apoptosis. Melittin, the key component of bee venom, is a potent inhibitor of calmodulin activity, and also a potent inhibitor cell growth and clonogenicity. Intracellular accumulation of melittin correlates with the cytotoxicity of antitumour agents. Previous studies indicated that some calcium antagonists and calmodulin inhibitors enhanced intracellular levels of antitumor agents by inhibiting their outward transport. In this study, treatment of exponentially growing HeLa and V79 cells with bleomycin caused a dose-dependent decrease in cell survival due to DNA damage. This lethal effect was potentiated by adding a non-lethal dose of the bee venom. By preventing repair of damaged DNA, bee venom inhibited recovery from potentially lethal damage induced by bleomycin in V79 and HeLa cells. Apoptosis, necrosis, and lysis were presumed as possible mechanisms by which bee venom inhibited growth and clonogenicity of V79 cells. HeLa cells, on the other hand, showed greater resistance to bee venom. Our findings suggest that bee venom might find a therapeutic use in enhancing cytotoxicity of antitumour agent bleomycin. U uvjetima in vitro istražen je inhibitorni u _inak p _elinjeg otrova, samog ili združenog s citostatikom bleomicinom, na rast stanica HeLa i V79. Rabljene su sljedeće metode: brojenje stanica, metoda klonskog rasta i apoptoza. Poznato je da neki antagonisti kalcija i kalmodulinski inhibitori povisuju unutarstani _nu razinu protutumorskih lijekova inhibirajući njihov prijenos iz stanice. Unutarstani _na akumulacija melitina izravno povećava citotoksi _ni u _inak protutumorskog lijeka. Obrada stanica HeLa i V79 u eksponencijalnoj fazi rasta bleomicinom uzrokuje oštećenje DNA ovisno o dozi te smanjenje broja živih stanica. Uo _eno je da se letalni u _inak bleomicina može poja _ati dodatkom neletalne doze p _elinjeg otrova. P _elinji otrov pritom inhibira popravak nastalih oštećenja u stanicama HeLa i V79 te sprje _ava oporavak stanica tretiranih bleomicinom. Apoptoza, nekroza i liza mogući su mehanizmi kojima p _elinji otrov inhibira rast i stvaranje kolonija stanica V79, dok HeLa-stanice pokazuju poja _anu otpornost na p _elinji otrov. Istraživanje također potvrđuje mogućnost uporabe p _elinjeg otrova u povećanju citotoksi _nosti bleomicina.
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