Glycyrol induces apoptosis in human Jurkat T cell lymphocytes via the Fas-FasL/caspase-8 pathway.
Glycyrrhiza uralensis (Leguminosae) has long been used to treat inflammatory ailments, such as gastric ulcers, arthritis, and rheumatism. From this traditional herbal plant, glycyrol, a coumestan with anti-bacterial and anti-inflammatory activities, was first isolated and synthesized to test its apoptosis-inducing properties in human Jurkat cells. Flow cytometry analysis indicated that glycyrol can arrest the cell cycle in S phase and subsequently induce apoptosis in both time- and dose-dependent manners. Consequently, it was shown that caspase-8 and -9 were involved in the activation of apoptosis after glycyrol treatment. Despite its known NF- κB inhibitory activity, glycyrol did not influence the prosurvival Bcl-2 and the proapoptotic Bax. Interestingly, glycyrol was revealed to enhance the Fas level independently from p53, which even slightly decreased. Thus, glycyrol acts in a similar manner as known cytostatic drugs and may have a potential as lead for the development of drugs for cancer treatment.
Shin
Eun Myoung
EM
Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
Kim
Sanghee
S
Merfort
Irmgard
I
Kim
Yeong Shik
YS
D017209:Apoptosis / Q000187:drug effects*; D053181:Caspase 8 / Q000378:metabolism*; D053453:Caspase 9 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D053222:Fas Ligand Protein / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D006035:Glycyrrhiza / Q000737:chemistry*; D006801:Humans; D019169:Jurkat Cells / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*; D019014:fas Receptor / Q000378:metabolism*
C491901:FAS protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D005419:Flavonoids; D010936:Plant Extracts; D019014:fas Receptor; C531349:glycyrol; D053181:Caspase 8; D053453:Caspase 9