Differential effect of sanguinarine, chelerythrine and chelidonine on DNA damage and cell viability in primary mouse spleen cells and mouse leukemic cells.
Sanguinarine, chelerythrine and chelidonine are isoquinoline alkaloids derived from the greater celandine. They possess a broad spectrum of pharmacological activities. It has been shown that their anti-tumor activity is mediated via different mechanisms, which can be promising targets for anti-cancer therapy. We focused our study on the differential effects of these alkaloids upon cell viability, DNA damage effect and nucleus integrity in mouse primary spleen cells and mouse lymphocytic leukemic cells, L1210. Sanguinarine and chelerythrine produce a dose-dependent increase in DNA damage and cytotoxicity in both primary mouse spleen cells and L1210 cells. Chelidonine did not show a significant cytotoxicity or damage DNA in both cell types, but completely arrested growth of L1210 cells. Examination of nuclear morphology revealed more cells with apoptotic features upon treatment with chelerythrine and sanguinarine, but not chelidonine. In contrast to primary mouse spleen cells, L1210 cells showed slightly higher sensitivity to sanguinarine and chelerythrine treatment. This suggests that cytotoxic and DNA damaging effects of chelerythrine and sanguinarine are more selective against mouse leukemic cells and primary mouse spleen cells, whereas chelidonine blocks proliferation of L1210 cells. The action of chelidonine on normal and tumor cells requires further investigation.
Kaminskyy
Vitaliy
V
Department of Regulation of Cell Proliferation and Apoptosis, Institute of Cell Biology, National Academy of Sciences, Drahomanov Street 14/16, 79005 Lviv, Ukraine.
Lin
Kah-Wai
KW
Filyak
Yevhen
Y
Stoika
Rostyslav
R
D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D053119:Benzophenanthridines / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D007546:Isoquinolines / Q000737:chemistry / Q000494:pharmacology*; D007938:Leukemia; D051379:Mice; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000187:drug effects
D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D053119:Benzophenanthridines; D007546:Isoquinolines; D010936:Plant Extracts; C062047:chelidonine; C005705:sanguinarine; C016299:chelerythrine