Kinetin inhibits growth of Helicobacter pylori by down-regulation of replication genes

H. pylori is a Gram-negative curved bacterium which primarily colonizes the epithelial layer of human stomach. Infection with this bacterium may lead to various gastric diseases from asymptomatic gastritis to gastric cancer. Because of its clinical importance, WHO designated H. pylori as a class I carcinogen. Kinetin is a type of cytokinins major role of which is to facilitate growth of the plants but it also plays a role to protect plants from infections. However, anti-bacterial effect of kinetin on H. pylori has not been elucidated. In this study, we performed agar dilution test and broth dilution test to determine MIC of kinetin against an H. pylori reference strain. In particular, we isolated H. pylori from gastric biopsies and confirmed inhibitory effect of kinetin against 60 clinical isolates of H. pylori. To elucidate the inhibitory mechanism of kinetin on H. pylori growth, we performed RT-PCR and found that kinetin down-regulated dnaA and holB expression both of which are necessary for bacterial replication. We also confirmed kinetin did not show cytotoxicity to gastric epithelial cells (AGS) with the dose completely inhibited H. pylori growth and kinetin did not inhibit the eukaryotic replication machinery. Moreover, kinetin reduced H. pylori-induced death of gastric cell line in vitro. Many recent reports are alarming the increased antibiotic resistance of H. pylori and limitation of current regimen for H. pylori eradication indicating necessity of new therapeutic agents. Although further studies seem to be necessary, our study collectively shows that kinetin inhibits growth of H. pylori by inhibiting replication of the bacteria and suggests kinetin as one of the potential candidates for H. pylori eradication.