Dulxanthone A induces cell cycle arrest and apoptosis via up-regulation of p53 through mitochondrial pathway in HepG2 cells.

Dulxanthone A induces cell cycle arrest and apoptosis via up-regulation of p53 through mitochondrial pathway in HepG2 cells. Research Abstract Details 

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Dulxanthone A induces cell cycle arrest and apoptosis via up-regulation of p53 through mitochondrial pathway in HepG2 cells. Abstract Text:

Ze Tian,Jie Shen,Annie P Moseman,Quanli Yang,Junshan Yang,Peigen Xiao,Erxi Wu,Isaac S Kohane,Ze Tian,Jie Shen,Annie P Moseman,Quanli Yang,Junshan Yang,Peigen Xiao,Erxi Wu,Isaac S Kohane,

Natural products derived from plants provide a rich source for development of new anticancer drugs. Dulxanthone A was found to be an active cytotoxic component in Garcinia cowa by bioactivity-directed isolation. Studies to elucidate the cytotoxic mechanisms of dulxanthone A showed that dulxanthone A consistently induced S phase arrest and apoptosis in the most sensitive cell line HepG2. Furthermore, p53 was dramatically up-regulated, leading to altered expression of downstream proteins upon dulxanthone A treatment. Cell cycle related proteins, such as cyclin A, cyclin B, cyclin E, cdc-2, p21 and p27 were down-regulated. Some apoptosis correlated proteins were also altered following the drug treatment. Bcl-2 family members PUMA was up-regulated while Bcl-2 and Bax were down-regulated. However, the expression ratio of Bax/Bcl-2 was increased. This resulted in the release of cytochrome C from the mitochondria to the cytosol. Concurrently, Apaf-1 was stimulated with p53 by dulxanthone A. In result, cytochrome C, Apaf-1 and procaspase-9 form an apoptosome, which in turn triggered the activation of caspase-9, caspase-3 and downstream caspase substrates. Lamin A/C and PARP were down-regulated or cleaved, respectively. Moreover, cell cycle arrest and apoptosis in HepG2 cells induced by dulxanthone A were markedly inhibited by siRNA knockdown of p53. In summary, dulxanthone A is an active cytotoxic component of G. cowa. It induces cell cycle arrest at lower concentrations and triggers apoptosis at higher concentrations via up-regulation of p53 through the intrinsic mitochondrial pathway in HepG2 cells. Dulxanthone A is therefore likely a promising preventive and/or therapeutic agent against Hepatoma.

Dulxanthone A induces cell cycle arrest and apoptosis via up-regulation of p53 through mitochondrial pathway in HepG2 cells. Publishing Authors By Initials

Z Tian,J Shen,AP Moseman,Q Yang,J Yang,P Xiao,E Wu,IS Kohane,Z Tian,J Shen,AP Moseman,Q Yang,J Yang,P Xiao,E Wu,IS Kohane,

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Dulxanthone A induces cell cycle arrest and apoptosis via up-regulation of p53 through mitochondrial pathway in HepG2 cells. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: International journal of cancer. Journal internati

VOLUME: 122

Page Numbers: 31-8

Journal Abbreviation: Int. J. Cancer

ISSN: 1097-0215

DAY: 1

MONTH: Jan

YEAR: 2008

Dulxanthone A induces cell cycle arrest and apoptosis via up-regulation of p53 through mitochondrial pathway in HepG2 cells. Information

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LANGUAGE: eng

NlmUniqueID: 42124

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Grant and Affiliation Information for Dulxanthone A induces cell cycle arrest and apoptosis via up-regulation of p53 through mitochondrial pathway in HepG2 cells.

AFFILIATION: Children's Hospital Informatics Program at Harvard- MIT Division of Health Sciences and Technology, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.

Country: United States

AGENCY: United States NLM

GRANT: 2TA5 LM 07092-11

ACRONYM: LM

MEDLINETA: Int J Cancer

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