Novel effects of glycyrrhetinic acid on the central nervous system tumorigenic progenitor cells: induction of actin disruption and tumor cell-selective toxicity.
Licorice extracts are used worldwide in foods and medicines, and glycyrrhetinic acid (GA) is a licorice component that has been reported to induce various important biological activities. In the present study, we show that GA induces actin disruption and has tumor cell-selective toxic properties, and that its selectivity is superior to those of all the clinically available antitumor agents tested. The cytotoxic activity of GA and the tested antitumor agents showed better correlation with the partition coefficient (log P) values rather than the polar surface area (PSA) values. For selective toxicity against tumor cells, GA was most effective at 10 microM that was the same concentration as the previously reported maximum plasma GA level reached in humans ingesting licorice. These results suggest that GA could be utilized as a promising chemopreventive and therapeutic antitumor agent. The underlying mechanisms involved in the selective toxicity to tumor cells by GA are also preliminarily discussed.
Yamaguchi
Hideaki
H
Department of Pharmacy, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tenpaku, Nagoya 468-8503, Japan. hyamagu@ccmfs.meijo-u.ac.jp
Noshita
Toshiro
T
Yu
Tao
T
Kidachi
Yumi
Y
Kamiie
Katsuyoshi
K
Umetsu
Hironori
H
Ryoyama
Kazuo
K
D000199:Actins / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002490:Central Nervous System / Q000473:pathology*; D016259:Genes, myc / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D006034:Glycyrrhetinic Acid / Q000494:pharmacology* / Q000633:toxicity; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000473:pathology*; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D014162:Transfection
D000199:Actins; D000970:Antineoplastic Agents; D006034:Glycyrrhetinic Acid