Učinci pčelinjega otrova i melitina na stanični odgovor tumorskih i ne-tumorskih stanica in vitro

doctoral thesis

• Title (english): Effects of bee venom and melittin on cell response of tumor and non-tumor cells in vitro
• Author: Goran Gajski
• Mentor: Vera Garaj-Vrhovac (mentor)
• Committee member: Nada Oršolić (član povjerenstva)
• Committee member: Vera Garaj-Vrhovac (član povjerenstva)
• Committee member: Maja Osmak (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2012, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology
• Universal decimal classification (UDC): 57 - Biological sciences. Physical anthropology. Biodiversity

Abstract

U ovom radu je istražen potencijalni protutumorski učinak pčelinjega otrova i njegove glavne sastavnice melitina prema različitim tipovima tumorskih stanica i njihovim sublinijama otpornima na citostatike kao i njihov učinak prema normalnim ne-tumorskim stanicama. Nakon obrade pčelinjim otrovom i melitinom sve stanine linije pokazale su citotoksini učinak koji je bio ovisan o dozi. Nadalje, obrada pčelinjim otrovom i melitinom uzrokovala je značajne morfološke promjene i staninu smrt uzrokovanu dominantno nekrozom. Nakon zajedničke obrade sa kemoterapeutikom cisplatinom, pčelinji otrov je pokazao aditivan učinak koji bi mogao biti koristan u vidu smanjivanja doze cisplatine za vrijeme kemoterapije. Također, pčelinji otrov i melitin uzrokovali su citotoksičnost i kod normalnih stanica uzrokujući smanjenje stanične vijabilnosti, morfološke promjene i oštećenja molekule DNA. Smanjenje glutationa i porast koncentracije malondialdehida, uz oksidativna oštećenja molekule DNA i porast aktivnosti fosfolipaze C, ukazuju da pčelinji otrov i melitin djeluju putem lipidne peroksidacije te da je oksidativni stres barem djelomično uključen u mehanizam djelovanja ovih spojeva. Iako toksičan kod svih ispitanih staninčih tipova, toksičnost pčelinjega otrova i melitina ovisna je o tipu stanica čineći tumorske stanice osjetljivijima na oba spoja naspram ne-tumorskih stanica. Ovisno o podrijetlu, stanice otporne na citostatike mogle bi biti osjetljivije na pčelinji otrov i melitin od svojih roditeljskih linija. Iako su se pokazali toksičnim kod svih ispitanih stanica, ovi rezultati idu u prilog upotrebe pčelinjega otrova i melitina u terapiji protiv tumora.

Abstract (english)

Possible anticancer ability of bee venom and its major component melittin towards different types of tumour cells and their drug resistant sublines as well as their impact on normal non-tumour cells was investigated. After the treatment with whole bee venom or melittin all the cell lines tested displayed dose dependent cytotoxicity. In addition, treatment with bee venom and melittin caused significant morphological changes and induced dominantly necrotic type of cell death. Following a combined treatment with chemotherapeutic drug cisplatin, bee venom exhibited additive effect what could be useful from the point of minimizing cisplatin concentration during chemotherapy. Bee venom and melittin were toxic to normal cells as well; causing lover cell viability, morphological cell alterations and DNA damage. Depletion of glutathione and increment in malondialdehid concentration parallel with oxidative DNA damage and induction of phospholipase C activity, suggest that both bee venom and melittin act through lipid peroxidation and that oxidative stress is at least partly involved in their mode of action. Although toxic to all cell types tested, toxicity of bee venom and melittin was cell type dependent making tumour cells more sensitive to both, as compared to the non-tumour cells. Depending on the origin, drug resistant cells could be more sensitive to bee venom and melittin than parental cells. Although toxic to all the cell lines tested, our results speak in favour of application of bee venom and melittin in anticancer therapy.

• Keywords: pčelinji otrov; melitin; cisplatina; citogenotoksičnost; oksidativni stres; tumorske stanice; ne-tumorske stanice
• Keywords (english): bee venom; melittin; cisplatin; cytogenotoxicity; oxidative stress; tumour cells; non-tumour cells
• Language: croatian
• URN:NBN: urn:nbn:hr:217:485424
• Study programme: Title: Biology; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija (doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2017-06-08 09:51:38