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Chung, Chang, Son, Park, Lim, Oh, Lee, and Park: Salvia miltiorrhiza Inhibits Tumor Cell Growth in Association with Rb Dephosphorylation through Up-regulation of p21 Via a p53-dependent Pathway
Original Article

Immune Network 2002; 2(1): 19-24.

Published online: 31 March 2002

DOI: https://doi.org/10.4110/in.2002.2.1.19

Salvia miltiorrhiza Inhibits Tumor Cell Growth in Association with Rb Dephosphorylation through Up-regulation of p21 Via a p53-dependent Pathway

Jin Chung1, Jae Eun Chang1, Yong Hae Son2, Hae Ruyn Park3, Suk Hwan Lim4, Yang Hyo Oh2, Moo Yeol Lee2, Yeong Min Park2

1Department of Microbiology, College of Dentistry, Pusan National University, Pusan, Korea.

2Department of Oral Pathology, College of Dentistry, Pusan National University, Pusan, Korea.

3Department of Microbiology and Immunology, College of Medicine, Pusan National University, Pusan, Korea.

4Department of Pediatrics, Mokpo Catholic Hospital, Korea.

Corresponding Author (immunpyn@pusan.ac.kr)

Copyright © 2002 The Korean Association of Immunologists

(open-access):

This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

BACKGROUND

Salvia miltiorrhiza (SM), a traditional oriental medicine, has been reported to have anti-tumor properties, but its exact mechanism remains to be elucidated. In this study, we investigated several of the molecular events that occur in human breast carcinoma MCF-7 cells and human pulmonary adenocarcinoma A549 cells.

METHODS

For this purpose, we evaluated the growth-inhibitory effect of SM in association with the expressions of p53, p21, cyclin D1, and pRb, which are known to be involved in cell cycle arrest. The extent of thymidine incorporation was also examined to assess G1/S phase cell cycle arrest in both cells by 3H-thymidine incorporation.

RESULTS

Our results show that SM inhibits the growth and the proliferation of MCF-7 and A549 cells. Furthermore, we also observed increased expression of p21 via a p53-dependent pathway in both cell lines after treating with SM. In addition, treatment with SM for 24 hours caused the suppression of hyperphosphorylated retinoblastoma protein (pRb) expression and the dephosphorylation of pRb.

CONCLUSIONS

These findings suggest that the growth inhibitory and the anti-proliferation effects of SM on MCF-7 cells and A549 cells are mediated via the decreased expression and dephosphorylation of pRB by p21 up-regulation in a p53-dependent manner. To the best of our knowledge, this study is the first to report upon the molecular mechanisms involved in SM-induced tumor cell growth inhibition.

Keywords: Salvia miltiorrhiza, p53, p21, pRb, MCF-7, A549

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