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Research ArticleExperimental Studies

Induction of Apoptosis in Human Hepatocellular Carcinoma Cells by Synthetic Antineoplaston A10

XIAN-JUN QU, SHU-XIANG CUI, ZHIGANG TIAN, XUN LI, MING-HUI CHEN, WEN-FANG XU, YOSHINORI INAGAKI, YING-BING DENG, MASATOSHI MAKUUCHI, MUNEHIRO NAKATA and WEI TANG
Anticancer Research July 2007, 27 (4B) 2427-2431;
XIAN-JUN QU
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SHU-XIANG CUI
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ZHIGANG TIAN
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XUN LI
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MING-HUI CHEN
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WEN-FANG XU
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YOSHINORI INAGAKI
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YING-BING DENG
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MASATOSHI MAKUUCHI
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MUNEHIRO NAKATA
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WEI TANG
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  • For correspondence: TANG-SUR@h.u-tokyo.ac.jp
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Abstract

Antineoplaston A10 (3-phenylacetylamino-2,6-piperidinedion) is a naturally occurring substance and was the first antineoplaston in the human body to be chemically identified. The effect of antineoplaston A10 on human hepatocellular carcinoma cell lines HepG2 and HLE has been examined. Antineoplaston A10 displayed anti-proliferative action inhibiting cell growth in a dose- and time-dependent manner in vitro as measured by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and clonogenic assays. Incubation with antineoplaston A10 for 48 h induced apoptotic events such as a typical apoptotic morphology, formation of a characteristic ladder pattern of DNA migration and accumulation of sub-G1 phase cells. Next, hepatoma xenografts in nude mice were employed to study the antitumor effects of antineoplaston A10 in vivo. Oral administration of antineoplaston A10 delayed the growth of HepG2 and HLE cells in the mice without a reduction in body weight. A higher proportion of apoptotic cells in xenografts was observed by means of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining. In addition, the level of expression of apoptotic marker p53 increased while that of anti-apoptotic protein bcl-2 decreased, as evaluated with immunohistochemical staining in the xenografts. These results suggested that antineoplaston A10 may inhibit the growth of human hepatoma cells through the induction of apoptosis.

  • Antineoplaston A10
  • hepatocellular carcinoma
  • apoptosis

Footnotes

  • Received January 24, 2007.
  • Accepted March 27, 2007.
  • Copyright© 2007 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved
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Anticancer Research: 27 (4B)
Anticancer Research
Vol. 27, Issue 4B
July-August 2007
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Induction of Apoptosis in Human Hepatocellular Carcinoma Cells by Synthetic Antineoplaston A10
XIAN-JUN QU, SHU-XIANG CUI, ZHIGANG TIAN, XUN LI, MING-HUI CHEN, WEN-FANG XU, YOSHINORI INAGAKI, YING-BING DENG, MASATOSHI MAKUUCHI, MUNEHIRO NAKATA, WEI TANG
Anticancer Research Jul 2007, 27 (4B) 2427-2431;

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Induction of Apoptosis in Human Hepatocellular Carcinoma Cells by Synthetic Antineoplaston A10
XIAN-JUN QU, SHU-XIANG CUI, ZHIGANG TIAN, XUN LI, MING-HUI CHEN, WEN-FANG XU, YOSHINORI INAGAKI, YING-BING DENG, MASATOSHI MAKUUCHI, MUNEHIRO NAKATA, WEI TANG
Anticancer Research Jul 2007, 27 (4B) 2427-2431;
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