Peripheral benzodiazepine receptor ligands induce apoptosis and cell cycle arrest in human hepatocellular carcinoma cells and enhance chemosensitivity to paclitaxel, docetaxel, doxorubicin and the Bcl–2 inhibitor HA14–1

2004 ◽  
Vol 42 (08) ◽  
Author(s):  
A Sutter ◽  
K Maaser ◽  
P Grabowski ◽  
M Höpfner ◽  
A Krahn ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Benzodiazepine Receptor ◽  
Carcinoma Cells ◽  
Peripheral Benzodiazepine Receptor ◽  
Receptor Ligands ◽  
Benzodiazepine Receptor Ligands ◽  
Cycle Arrest ◽  
Human Hepatocellular Carcinoma Cells

Synergistic Effect of α-Solanine and Cisplatin Induces Apoptosis and Enhances Cell Cycle Arrest in Human Hepatocellular Carcinoma Cells

2020 ◽  
Vol 19 (18) ◽  
pp. 2197-2210 ◽  
Author(s):  
Sherien M. El-Daly ◽  
Shaimaa A. Gouhar ◽  
Amira M. Gamal-Eldeen ◽  
Fatma F. Abdel Hamid ◽  
Magdi N. Ashour ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Synergistic Effect ◽  
Cell Cycle Arrest ◽  
Combination Treatment ◽  
Carcinoma Cells ◽  
Cell Growth Inhibition ◽  
Cycle Arrest ◽  
Induced Apoptosis ◽  
Human Hepatocellular Carcinoma Cells

Aim: The clinical application of cisplatin is limited by severe side effects associated with high applied doses. The synergistic effect of a combination treatment of a low dose of cisplatin with the natural alkaloid α-solanine on human hepatocellular carcinoma cells was evaluated. Methods: HepG2 cells were exposed to low doses of α-solanine and cisplatin, either independently or in combination. The efficiency of this treatment modality was evaluated by investigating cell growth inhibition, cell cycle arrest, and apoptosis enhancement. Results: α-solanine synergistically potentiated the effect of cisplatin on cell growth inhibition and significantly induced apoptosis. This synergistic effect was mediated by inducing cell cycle arrest at the G2/M phase, enhancing DNA fragmentation and increasing apoptosis through the activation of caspase 3/7 and/or elevating the expression of the death receptors DR4 and DR5. The induced apoptosis from this combination treatment was also mediated by reducing the expression of the anti-apoptotic mediators Bcl-2 and survivin, as well as by modulating the miR-21 expression. Conclusion: Our study provides strong evidence that a combination treatment of low doses of α-solanine and cisplatin exerts a synergistic anticancer effect and provides an effective treatment strategy against hepatocellular carcinoma.

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