Kaminskyy V. Mechanisms of apoptosis induction in lymphoma cells by greater celandine alkaloids.

Українська версія

Thesis for the degree of Candidate of Sciences (CSc)

State registration number

0406U004363

Applicant for

Specialization

  • 03.00.11 - Цитологія, гістологія

18-10-2006

Specialized Academic Board

Д 35.246.01

Institute of Cell Biology

Essay

Object - mechanisms of lymphoma cells death. The aim of the study - study on the molecular and cell level of the mechanisms of apoptosis induction in lymphoma cells by the main celandine alkaloids - chelidonine, sanguinarine, chelerythrine and coptisine. Methods: biochemical, statistical. Chelidonine, sanguinarine, chelerythrine and coptisine induced a mitochondrial type of apoptosis. These alkaloids induced cytochrome c release from the mitochondrial membrane into the cytoplasm, where it activated initiator caspase-9 and effector caspase-3. Another type of apoptosis was realized by alkaloids via an activation of receptor-dependent initiator caspase-8 in the lymphoma cells. The main mechanisms of cell death induction by sanguinarine, chelerythrine and coptisine are their intercalation into the structure of DNA and their effect on the function of mitochondria. Sanguinarine and chelerythrine induced single- and double-strand DNA breaks, decreased mitochondrial trans-membrane potential and ATP level at the early stages of their action. Chelidonine had no ability to intercalate into the structure of DNA of lymphoma cells, arrest cells in G2/M phases of cell cycle. Area of use - cell biology, pharmacology.

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