cyclin-d1 and lycorine

Topics: Amaryllidaceae Alkaloids; Apoptosis; Cell Line, Tumor; Cell Proliferation; Cyclin D1; Down-Regulation; Humans; Phenanthridines; Stomach Neoplasms

To investigate the antitumor effect of lycorine on renal cell carcinoma ACHN cells and explore the possible mechanism.. We used flow cytometry to examine the effect of lycorine on ACHN cell cycle and apoptosis. The cell proliferation, migration and invasion were assessed with MTS assay, wound healing assay, and Transwell assay, respectively. Colony forming assay was performed, and the mRNA and protein levels of Bax, Bcl-2, survivin, caspase-3, cyclin D1 and CDK4 were measured with qRT-PCR and Western blotting.. Lycorine obviously inhibited the proliferation of ACHN cells with an IC(50) of 24.34 µmol/L. Lycorine also induced apoptosis of ACHN cells, caused cell cycle arrest at G(0)/G(1) phase, and suppressed the colony forming ability of the cells in a dose-dependent manner. The migration and invasion of ACHN cells were significantly inhibited by 5 µmol/L lycorine. Lycorine up-regulated the mRNA levels of CDK4, Bax, caspase-3 while down-regulated the levels of survivin, Bcl-2 and Cyclin D1; the protein levels of CDK4 and Bax were increased and cyclin D1, Bcl-2 and surviving expressions were decreased, but caspase-3 expression showed no significant changes following the treatment.. Lycorine has obvious antitumor effect against ACHN cells, suggesting its value as a new therapeutic agent for renal cell carcinoma.

Topics: Amaryllidaceae Alkaloids; Antineoplastic Agents, Phytogenic; Apoptosis; bcl-2-Associated X Protein; Carcinoma, Renal Cell; Caspase 3; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Cyclin D1; Cyclin-Dependent Kinase 4; Humans; Inhibitor of Apoptosis Proteins; Phenanthridines; Proto-Oncogene Proteins c-bcl-2; Survivin

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.

Topics: Amaryllidaceae Alkaloids; Antineoplastic Agents; Apoptosis; bcl-2-Associated X Protein; Caspases; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cyclin D1; Cyclin-Dependent Kinase 4; Cytochromes c; Gene Expression Regulation, Neoplastic; Humans; Multiple Myeloma; Phenanthridines; Plant Extracts; Proto-Oncogene Proteins c-bcl-2