Nicotinic acid inducing G0/G1 cell cycle arrest and apoptosis in Ehrlich ascites carcinoma cells in vivo

Abstract

Niacin, nicotinic acid; (NA), is a water-soluble vitamin (vitamin B3) which serves as a precursor of nicotinamide adenine dinucleotide and is one of the premier lipid lowering agents for treatment of cardiovascular diseases. Aims: the aim of the present study was to evaluate whether treatment with nicotinic acid has antitumor effect on the Ehrlich ascites carcinoma (EAC) cells. Methods: Female Swiss albino mice were transplanted with EAC cells and treated one day later with nicotinic acid at 50mg/mouse, orally (NA-50), nicotinic acid at 100mg/mouse, orally (NA-100) and cisplatin at 40 µg/mouse, i.p. (CIS-40) as a reference drug, all groups were treated for six consecutive days. At day 7, mice were euthanized and EAC cells were harvested, counted and the gene expression levels of the NA receptor GPR109A were analyzed in the EAC cells by RT-PCR Results: Mice treated with NA-100 showed significant reduction in the EAC cell number as compared to treatment with NA-50. This anti-tumor effect of 100mg NA was still lower than treatment with 40 µg CIS which induced killing of most EAC cells. Although the EAC cell number in NA-100 treated group lower than those induced by CIS, the NA-100 induced antitumor effect was mediated by arresting the G1 phase of EAC cell cycle as measured by flow cytometry. As demonstrated by higher percentage of cells in the sub-G1 phase in that group. GPR109A expression level was higher in NA-100 treated group than in CIS treated group. Conclusion: NA has antitumor and anti-proliferative effects on Ehrlich tumor in ascitic form as demonstrated by arresting the cell cycle of EAC-cells through increasing the expression GPR109A.