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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
Published on: December 27, 2016
Apoptosis induced by lycorine in KM3 cells is associated with the G0/G1 cell cycle arrest
Yan Li1, Jing Liu, Li-Jun Tang
1Molecular Biology Research Center, School of Biological Science and Technology, Central South University, Hunan 410078, P.R. China.
Abstract:
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.
Insights
Lycorine, a natural anti-tumor compound, effectively inhibits human multiple myeloma (KM3) cell proliferation. It induces apoptosis and arrests the cell cycle, offering potential therapeutic strategies.
Area of Science:
- Natural Products Chemistry
- Molecular Biology
- Cancer Research
Background:
- Lycorine is a bioactive alkaloid derived from Amaryllidaceae plants.
- It exhibits known biological activities against various malignant cells.
Purpose of the Study:
- To investigate the anti-cancer effects of lycorine on the human multiple myeloma cell line KM3.
- To elucidate the underlying mechanisms of lycorine-induced cell death and cell cycle arrest.
Main Methods:
- MTT assay to assess cell viability and proliferation.
- Flow cytometry to detect apoptosis and cell cycle distribution.
- Western blot analysis to examine key proteins involved in apoptosis and cell cycle regulation.
Main Results:
- Lycorine demonstrated significant inhibitory activity against KM3 cells, reducing their growth rates.
- Apoptosis was induced, evidenced by morphological changes, DNA fragmentation, and a sub-G1 peak.
- Lycorine triggered the mitochondrial and death receptor pathways, involving cytochrome c release and caspase activation.
- The cell cycle was arrested at the G0/G1 phase, associated with decreased cyclin D1 and CDK4 expression.
Conclusions:
- Lycorine effectively suppresses proliferation and enhances apoptosis in human multiple myeloma cells.
- Mechanisms include cell cycle arrest at G0/G1 and activation of intrinsic and extrinsic apoptotic pathways.
- Lycorine shows promise as a potential therapeutic agent for multiple myeloma.
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