HY253, a Novel Decahydrofluorene Analog, Induces Apoptosis via Intrinsic Pathway and Cell Cycle Arrest in Liver Cancer HepG2 Cells

Title
HY253, a Novel Decahydrofluorene Analog, Induces Apoptosis via Intrinsic Pathway and Cell Cycle Arrest in Liver Cancer HepG2 Cells
Author
서혜원
Keywords
Aralia continentalis; apoptosis; p27KIP1; p21CIP1; cytochrome c; HepG2
Issue Date
2015-03
Publisher
한국미생물생명공학회
Citation
JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY, v. 25, No. 3, Page. 413-417
Abstract
Recently, we isolated HY253, a novel decahydrofluorene analog with a molecular structure of 7,8a-divinyl-2,4a,4b,5,6,7,8,8a,9,9a-decahydro-1H-fluorene-2,4a,4b,9a-tetraol from the roots of Aralia continentalis, which is known as Dokwhal ( ), a traditional medicinal herb. Moreover, we previously reported its cytotoxic activity on cancer cell proliferation in human lung cancer A549 and cervical cancer HeLa cells. The current study aimed to evaluate its detailed molecular mechanisms in cell cycle arrest and apoptotic induction in human hepatocellular carcinoma HepG2 cells. Flow cytometric analysis of HepG2 cells treated with 60 μM HY253 revealed appreciable cell cycle arrest at the G1 phase via inhibition of Rb phosphorylation and down-regulation of cyclin D1. Furthermore, using western blots, we found that up-regulation of cyclin-dependent kinase inhibitors, such as p21CIP1 and p27KIP1, was associated with this G1 phase arrest. Moreover, TUNEL assay and immunoblottings revealed apoptotic induction in HepG2 cells treated with 100 μM HY253 for 24 h, which is associated with cytochrome c release from mitochondria, via down-regulation of anti-apoptotic Bcl-2 protein, which in turn resulted in activation of caspase-9 and -3, and proteolytic cleavage of poly(ADP-ribose) polymerase (PARP). Accordingly, we suggest that HY253 may be a potent chemotherapeutic hit compound for treating human liver cancer cells via up-regulation and activation of the p53 gene.
URI
http://kiss.kstudy.com/thesis/thesis-view.asp?key=3311291http://repository.hanyang.ac.kr/handle/20.500.11754/106001
ISSN
1017-7825; 1738-8872
Appears in Collections:
RESEARCH INSTITUTE[E](부설연구소) > INSTITUTE OF PHARMACEUTICAL SCIENCE AND TECHNOLOGY(약학기술연구소) > Articles
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