[Frontiers in Bioscience E2, 221-230, January 1, 2010]

Bing De Ling®, a Chinese herbal formula, inhibits cancer cells growth via p53

Yingtao Zhang1, Huiqin Dong1, Zhenyu Li2, Shengyan Xiang1, Yuyan Zhu1, Mu Zhang1, Jing Liu4, Wenlong Bai1,2, Santo V. Nicosia 1, 3, Jiandong Chen2, Ruan-Jin Zhao , Xiaohong Zhang1,2

1Department of Pathology and Cell Biology, USF College of Medicine, 2Programs of Molecular Oncology, 3Experimental Therapeutics, H. Lee Moffitt Cancer Center, Tampa, Florida 33612-4799, 4The Center for Traditional Chinese Medicine Inc., 1299 South Tamiami Trail, Sarasota, Florida 34239

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Materials and methods
3.1. Herbal medicine
3.2. Cell lines and plasmids
3.3. MTT assays
3.4. Cell cycle analysis
3.5. Immunoblotting analysis
3.6. Transfection and luciferase reporter assays
3.7. ELISA (enzyme-linked immunosorbent assay)
4. Results and discussion
4.1. Bing De Ling® induces growth inhibition in p53-positive ovarian cancer surface epithelial cells
4.2. Bing De Ling® induces G1 arrest in OV2008 cells
4.3. Bing De Ling® regulates the protein levels of cell cycle-related genes
4.4. Bing De Ling® upregulates p53 protein level, its transcriptional activities and its downstream target genes
4.5. Bing De Ling® induces growth inhibition in OV2008 ovarian carcinoma cells via p53
4.6. Bing De Ling® disrupts MDMX-p53 interaction
5. Acknowledgment
6. References

1. ABSTRACT

Bing De Ling® is a Chinese herbal formula that has been used to treat cancer patients for more than a decade. However, the molecular mechanisms behind its anti-tumor efficacy are still elusive. Here, we show that Bing De Ling® inhibits cell proliferation in ovarian cancer epithelial cell lines, OV2008 and C13. It induces G1/S arrest in a p53-dependent manner in that this effect is attenuated in OV2008 cells transfected with dominant-negative p53 plasmid. Moreover, we show that Bing De Ling® up-regulates p53 transcriptional activities as well as its downstream target genes, such as p21Cip1, MDM2, and MDMX. In addition, Bing De Ling® inhibits MDMX-p53 interaction which may result in stabilization and activation of p53. Collectively, our results suggest that the anti-tumor activity of Bing De Ling® may be in part due to activation of p53.