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Mol. Cells 2001; 12(1): 17-24

Published online August 31, 2001

© The Korean Society for Molecular and Cellular Biology

Induction of Apoptosis in p53-Deficient Human Hepatoma Cell Line by Wild-Type p53 Gene Transduction: Inhibition by Antioxidant

Kee-Ho Lee, Keun-Cheol Kim, Yu-Jin Jung, Yong-Ho Ham, Ja-June Jang, Heechung Kwon

Abstract

We investigated the role of wild-type (wt)-p53 as an inducer of apoptotic cell death in human hepatoma cell lines. Following the retrovirus-mediated transduction of the wt-p53 gene, Hep3B cells lacking the endogenous p53 expression began to die through apoptosis in 4 h. They showed a maximal apoptotic death at 12 h, whereas HepG2 cells expressing endogenous p53 did not. However, the transduction of the wt-p53 gene elicited growth suppression of both Hep3B and HepG2 cells. P21WAF1/CIP1, a p53-inducible cell cycle inhibitor, was induced, not only in Hep3B cells undergoing apoptosis, but also in HepG2 cells. The kinetics of the p21WAF1/CIP1 induction, DNA fragmentation, and growth suppression of the Hep3B cells showed that DNA fragmentation and growth suppression progressed rapidly following p21WAF1/CIP1 accumulation. N-acetyl-cysteine or glutathione, potent antioxidants, strongly inhibited the DNA fragmentation, but did not reduce the elevated level of p21WAF1/CIP1. These findings suggested that p21WAF1/CIP1 was not a critical mediator for the execution of p53-mediated apoptosis, although it contributed to the growth inhibition of cells undergoing apoptosis. Furthermore, p53-mediated apoptosis could be repressed by antioxidants.

Keywords Apoptosis, p53, : p21WAF1/CIP1, Hepat, Antioxidant

Article

Research Article

Mol. Cells 2001; 12(1): 17-24

Published online August 31, 2001

Copyright © The Korean Society for Molecular and Cellular Biology.

Induction of Apoptosis in p53-Deficient Human Hepatoma Cell Line by Wild-Type p53 Gene Transduction: Inhibition by Antioxidant

Kee-Ho Lee, Keun-Cheol Kim, Yu-Jin Jung, Yong-Ho Ham, Ja-June Jang, Heechung Kwon

Abstract

We investigated the role of wild-type (wt)-p53 as an inducer of apoptotic cell death in human hepatoma cell lines. Following the retrovirus-mediated transduction of the wt-p53 gene, Hep3B cells lacking the endogenous p53 expression began to die through apoptosis in 4 h. They showed a maximal apoptotic death at 12 h, whereas HepG2 cells expressing endogenous p53 did not. However, the transduction of the wt-p53 gene elicited growth suppression of both Hep3B and HepG2 cells. P21WAF1/CIP1, a p53-inducible cell cycle inhibitor, was induced, not only in Hep3B cells undergoing apoptosis, but also in HepG2 cells. The kinetics of the p21WAF1/CIP1 induction, DNA fragmentation, and growth suppression of the Hep3B cells showed that DNA fragmentation and growth suppression progressed rapidly following p21WAF1/CIP1 accumulation. N-acetyl-cysteine or glutathione, potent antioxidants, strongly inhibited the DNA fragmentation, but did not reduce the elevated level of p21WAF1/CIP1. These findings suggested that p21WAF1/CIP1 was not a critical mediator for the execution of p53-mediated apoptosis, although it contributed to the growth inhibition of cells undergoing apoptosis. Furthermore, p53-mediated apoptosis could be repressed by antioxidants.

Keywords: Apoptosis, p53, : p21WAF1/CIP1, Hepat, Antioxidant

Mol. Cells
Aug 31, 2022 Vol.45 No.8, pp. 513~602
COVER PICTURE
Cryo-EM structure of human porphyrin transporter ABCB6 (main figure) shows that binding of hemin (inset, magenta) in concert with two glutathione molecules (cyan) primes ABCB6 for high ATP turnover (Kim et al., pp. 575-587).

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