(-)-Menthol inhibits DNA topoisomerases I, II alpha and beta and promotes NF-kappaB expression in human gastric cancer SNU-5 cells.
It has been reported that (-)-Menthol can inhibit the growth of rat liver epithelial tumor cells and is a potent chemopreventive agent. The purpose of the present experiment was to examine and identify cellular processes leading to cell death which are affected by (-)-Menthol in human gastric SNU-5 cancer cells. Cell death (cytotoxicity) was examined and analyzed by trypan blue stain and flow cytometric methods. It was shown that (-)-Menthol inhibited the proliferation of the cells in a dose- and time-dependent manner, inhibited topoisomerase I, IIa and IIbeta, but promoted the levels of NF-kappaB gene expression based on the Western blot and polymerase chain reaction (PCR) and cDNA microarray methods. These data suggest that (-)-Menthol may induce cytotoxicity through inhibiting gene expression of topoisomerase I, IIalpha and IIbeta and promoting the gene expression of NF-kappaB in SNU-5 cells.
Lin
Jing-Pin
JP
School of Chinese Medicine and Department of Microbiology, China Medical University, Taichung City, 400, Taiwan.
Lu
Hsu-Feng
HF
Lee
Jau-Hong
JH
Lin
Jaung-Gung
JG
Hsia
Te-Chun
TC
Wu
Lii-Tzu
LT
Chung
Jing-Gung
JG
D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D026942:DNA Topoisomerases / Q000096:biosynthesis / Q000235:genetics; D004264:DNA Topoisomerases, Type I / Q000096:biosynthesis / Q000235:genetics; D004250:DNA Topoisomerases, Type II / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D008610:Menthol / Q000494:pharmacology*; D016328:NF-kappa B / Q000096:biosynthesis* / Q000235:genetics; D013237:Stereoisomerism; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D059003:Topoisomerase Inhibitors
D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D016328:NF-kappa B; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D059003:Topoisomerase Inhibitors; D008610:Menthol; D026942:DNA Topoisomerases; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II