Taiwanin A induced cell cycle arrest and p53-dependent apoptosis in human hepatocellular carcinoma HepG2 cells.
Taiwanin A, a lignan isolated from Taiwania cryptomerioides Hayata, has previously been reported to have cytotoxicity against human tumor cells, but the mechanisms are unclear. In this study, we examined the molecular mechanism of cell death of human hepatocellular carcinoma HepG2 cells induced by Taiwanin A. Taiwanin A has been found to induce cell cycle arrest at G2/M phase as well as caspase-3-dependent apoptosis within 24 h. We performed both in vitro turbidity assay and immunofluorescence staining of tubulin to show that Taiwanin A can inhibit microtubule assembly. Moreover, the tumor suppressor protein p53 in HepG2 cells was activated by Taiwanin A within 12 h. Inhibition of p53 by either pifithrin-alpha or by short hairpin RNA which blocks p53 expression attenuates Taiwanin A cytotoxicity. Our results demonstrate that Taiwanin A can act as a new class of microtubule damaging agent, arresting cell cycle progression at mitotic phase and inducing apoptosis through the activation of p53.
Ho
Pai-Jiun
PJ
Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan, ROC.
Chou
Chen-Kung
CK
Kuo
Yueh-Hsiung
YH
Tu
Lan-Chun
LC
Yeh
Sheau-Farn
SF
D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005663:Furans / Q000494:pharmacology*; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000473:pathology; D008868:Microtubule Proteins / Q000378:metabolism; D008941:Spindle Apparatus / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D005663:Furans; D017705:Lignans; D008868:Microtubule Proteins; D016159:Tumor Suppressor Protein p53; C419332:taiwanin A