Tetrandrine and caffeine modulated cell cycle and increased glioma cell death via caspase-dependent and caspase-independent apoptosis pathways.

Abstract

Viability, cell cycle distribution, and expressions of eukaryotic translation initiation factor-2α (eIF-2α), cyclin D1, poly(ADP-ribose) polymerase 1 (PARP-1), and apoptosis-inducing factor (AIF) of RT-2 glioma cells were assayed under treatment of tetrandrine and caffeine for 48 h. The results showed that cell viability decreased significantly under treatment with tetrandrine (5 μM) alone or under combined treatment with tetrandrine (5 μM) and caffeine (0.5 or 1 mM). The ratio of RT-2 cells at sub G1 and G0/G1 stages increased significantly during combined treatment of tetrandrine (5 μM) and caffeine (0.5, 1 mM). The ratio of phospharylated eIF-2α to dephospharylated eIF-2α increased, whereas cyclin D1 decreased significantly under combined treatment of tetrandrine (5 μM) and caffeine (1 mM). The cleaved PARP-1 to PARP-1 ratio was elevated significantly under treatment of 5 μM tetrandrine alone, and combined treatment of 5 μM tetrandrine and caffeine (0.5, 1 mM). The expression levels of AIF increased significantly under treatment of 5 μM tetrandrine alone or 1 mM caffeine alone, and combined treatment of 5 μM tetrandrine and caffeine (0.5, 1 mM). In conclusion, tetrandrine and caffeine could induce glioma cell death possibly via increasing eIF-2α phospharylation, decreasing cyclin-D1 expression, and increasing caspase-dependent and -independent apoptosis pathways.

• Authors: Jin-Cherng Chen, Juen-Haur Hwang, Wen-Hsuan Chiu, Yin-Ching Chan
• Journal: Nutrition and cancer (Nutr Cancer) Vol. 66 Issue 4 Pg. 700-6 ( 2014) ISSN: 1532-7914 [Electronic] United States
• PMID: 24738643 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aifm1 protein, rat
• Apaf1 protein, rat
• Apoptosis Inducing Factor
• Apoptotic Protease-Activating Factor 1
• Benzylisoquinolines
• Ccnd1 protein, rat
• Eukaryotic Initiation Factor-2
• Cyclin D1
• tetrandrine
• Caffeine
• Parp1 protein, rat
• Poly (ADP-Ribose) Polymerase-1
• Poly(ADP-ribose) Polymerases
• Casp3 protein, rat
• Caspase 3

Topics

• Animals
• Apoptosis (drug effects)
• Apoptosis Inducing Factor (genetics, metabolism)
• Apoptotic Protease-Activating Factor 1 (genetics, metabolism)
• Benzylisoquinolines (pharmacology)
• Caffeine (pharmacology)
• Caspase 3 (genetics, metabolism)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Survival
• Cyclin D1 (genetics, metabolism)
• Eukaryotic Initiation Factor-2 (metabolism)
• Glioma (metabolism, pathology)
• Phosphorylation
• Poly (ADP-Ribose) Polymerase-1
• Poly(ADP-ribose) Polymerases (genetics, metabolism)
• Rats
• Rats, Inbred F344
• Signal Transduction (drug effects)