The molecular mechanisms of nicotinamide adenine dinucleotide in inhibiting human liver cells from apoptosis induced by cisplatin

Nicotinamide Adenine Dinucleotide (NADH) plays a primary role in the energy production in human cells. NADH is involved in cellular DNA repair. Chemot herapy for cancer often has severe side effects that limit its efficacy. Th e objective of this study was to elucidate molecular mechanisms of NADH in inhibiting apoptosis of human normal cells induced by chemotherapy drugs an d identify NADH as a kind of chemotherapy protection factor. In cells treat ed with NADH and Cisplatin, no typical apoptotic morphological changes of c ells were observed compared with cells treated with Cisplatin alone. Flow c ytometry indicated the apoptotic rate of cells were as follows: 11.2%, 24.3 %, 51.8% and 89.4%, when cells were treated with 10 mu M Cisplatin for 12h to 48h. In contrast with the group of Cisplatin, the apoptotic rate of cell s in the group of NADH and Cisplatin decreased to 5.7%, 10.8%, 11.2% and 13 .1%. Compared with Cisplatin treated cells, p53 mRNA expression decreased a nd Bcl-2 mRNA expression increased in the cells treated with NADH and Cispl atin. Caspase-3 activity raised quickly when cells were incubated with 1 mu m Cisplatin especially after 24h. However, if cells were cultured with NAD H then with Cisplatin, Caspase-3 activity was kept in a low level. The alte ration of Caspase-8 appeared to be similar to caspase-3. Our results showed NADH may inhibit human liver cells from apoptosis. These findings may rais e the possibility of using NADH to reduce the side effects of chemotherapy for human cancer.