Correction of malignant behavior of tumor cells by traditional Chinese herb medicine through a restoration of p53 Win-Ping Deng a, * , Ming-Wei Chao a , Wen-Fu Lai a , Chi Sun b , Chen-Yen Chung a , Cheng-Chia Wu a , I-Hsin Lin c , Jeng-Jong Hwang d , Chiu-Hsiung Wu e , Wen-Ta Chiu f , Chia-Yu Chen a , John-Leslie Redpath b a Institute of Biomedical Materials, Taipei Medical University, 250, Wu-Hsing Street, 110 Taipei, Taiwan, ROC b Department of Radiation Oncology, University of California at Irvine, Irvine, CA, USA c Institute of Traditional Medicine, Chung-Gung University, Taipei, Taiwan, ROC d Institute of Radiological Sciences, National Yang-Ming University, Taipei, Taiwan, ROC e Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan, ROC f Taipei Municipal Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan, ROC Received 6 February 2005; received in revised form 14 March 2005; accepted 17 March 2005 Abstract We have previously demonstrated that a UVC-induced tumorigenic HeLa x skin fibroblast cell line could be induced to form a more normal phenotypic state (‘reversion’), including loss of IAP expression. We have now used the loss of IAP expression to monitor the enhancement of this reversion in the cervical cancer cell line, HeLa, by a traditional Chinese herb medicine (TCM), Yigan Kang (YGK). IAP level decreased, and the reversion frequency increased, in a dose-dependent manner at concentrations of YGK of more than 10 mg. YGK significantly repressed E6/E7 oncogenes at the transcriptional level, with subsequent reactivation of p53 and p21 expression (P!0.01). YGK had little effect on the cell cycle of HeLa cells and slightly increased the apoptotic cell death between 20 and 40 mg. In vivo, tumorigenicity studies were performed using six different animal experimental protocols, which demonstrated that YGK was effective at inducing reversion of the tumorigenic phenotype, with YGK-treated HeLa cells showing much less aggressive tumor growth than untreated cells. YGK may raise the possibility of the continuing management of some cancers as a chronic condition in which the malignant behavior of the tumor cells is constrained. q 2005 Elsevier Ireland Ltd. All rights reserved. Keywords: Cancer reversion; TCM; IAP; p53; HPV; Yigan Kang 1. Introduction Neoplastic transformation of normal cells can occur spontaneously or can be induced by viruses, chemical carcinogens, or irradiation. Such trans- formed cells, however, can also spontaneously, or be Cancer Letters 233 (2006) 315–327 www.elsevier.com/locate/canlet 0304-3835/$ - see front matter q 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.canlet.2005.03.031 * Corresponding author. Tel.: C886 2 2739 0863; fax: C886 2 2739 5584. E-mail address: wpdeng@ms41.hinet.net (W.-P. Deng).