Apoptosis induced by lycorine in KM3 cells is associated with the G0/G1 cell cycle arrest.
Lycorine is a natural anti-tumor alkaloid extracted from Amaryllidaceae and has various biological effects on malignant cells. The present study explores the effects of lycorine on the human multiple meyloma cell line, KM3, and the possible mechanisms of these effects. An MTT assay showed that lycorine had significant inhibitory activity on KM3 cells. The growth rates of the KM3 cells exposed to lycorine evidently slowed down. Cell fluorescent apoptotic morphological changes, DNA degradation fragments, and a sub-G1 peak were detected, indicating the occurrence of cell apoptosis after lycorine treatment. Furthermore, the release of mitochondrial cytochrome c, the augmentation of Bax with the attenuation of Bcl-2, and the activation of caspase-9, -8, and -3 were also detected, suggesting that the mitochondrial pathway and the death acceptor pathway were also involved. The results also showed that lycorine was able to block the cell cycle at the G0/G1 phase through the downregulation of both cyclin D1 and CDK4. In summary, lycorine can suppress the proliferation of KM3 cells and reduce cell survival by arresting cell cycle progression as well as inducing cell apoptosis.
Li
Yan
Y
Molecular Biology Research Center, School of Biological Science and Technology, Central South University, Hunan 410078, P.R. China.
Liu
Jing
J
Tang
Li-Jun
LJ
Shi
Yi-Wu
YW
Ren
Wei
W
Hu
Wei-Xin
WX
D047151:Amaryllidaceae Alkaloids / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D020169:Caspases / Q000096:biosynthesis; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000096:biosynthesis; D051358:Cyclin-Dependent Kinase 4 / Q000096:biosynthesis; D045304:Cytochromes c / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy*; D010617:Phenanthridines / Q000494:pharmacology*; D010936:Plant Extracts / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D047151:Amaryllidaceae Alkaloids; D000970:Antineoplastic Agents; D010617:Phenanthridines; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D019938:Cyclin D1; D045304:Cytochromes c; D051358:Cyclin-Dependent Kinase 4; D020169:Caspases; C015330:lycorine