Growth inhibition and G1 cell cycle arrest mediated by 25-methoxyhispidol A, a novel triterpenoid, isolated from the fruit of Poncirus trifoliata in human hepatocellular carcinoma cells.
Poncirus trifoliata (Rutaceae) extracts have been known to possess anti-allergic, anti-inflammatory and antiviral activities. However, other biological activities, especially, the anticancer potential of extracts of P. trifoliata or its constituents, have not been fully investigated yet. In this study, we have evaluated the antiproliferative effects of a novel triterpenoid, 25-methoxyhispidol A, isolated from the fruit of P. trifoliata against SK-HEP-1 human hepatocellular carcinoma cells. Flow cytometric analysis indicated that 25-methoxyhispidol A arrests the cell cycle in the G1 phase at the earlier time and subsequently induces apoptosis of the cancer cells. Further study revealed that the cell cycle arrest in the G1 phase by 25-methoxyhispidol A correlated well with the inhibition of phosphorylation of the retinoblastoma (Rb) protein, and with the down-regulation of cyclin D1 and cyclin-dependent kinase cdk4 and the induction of cdk inhibitor p21 (WAF1/Cip1) protein. These findings suggest the potential of 25-methoxyhispidol A isolated from the fructus of P. trifoliata as an antitumor agent against human hepatocarcinoma cells by arresting the cell cycle and inducing apoptosis.
Hong
Ji- Young
J
College of Pharmacy, Ewha Womans University, Seoul, Korea.
Min
Hye-Young
HY
Xu
Guang Hua
GH
Lee
Jong-Gu
JG
Lee
Seung-Ho
SH
Kim
Young Shik
YS
Kang
Sam Sik
SS
Lee
Sang Kook
SK
D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D005638:Fruit; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D018514:Plant Structures / Q000633:toxicity; D032104:Poncirus; D014315:Triterpenes / Q000302:isolation & purification / Q000494:pharmacology*
D000970:Antineoplastic Agents; D010936:Plant Extracts; D014315:Triterpenes