Rhein lysinate induces apoptosis in breast cancer SK-Br-3 cells by inhibiting HER-2 signal pathway.
- Author:
Ya-Jun LIN
1
;
Yun-Hong HUANG
;
Yong-Zhan ZHEN
;
Xiu-Jun LIU
;
Yong-Su ZHEN
Author Information
1. Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
- Publication Type:Journal Article
- MeSH:
Anthraquinones;
pharmacology;
Antineoplastic Agents;
pharmacology;
Apoptosis;
drug effects;
Breast Neoplasms;
metabolism;
pathology;
Cell Line, Tumor;
Cell Proliferation;
drug effects;
Cyclin-Dependent Kinase Inhibitor p21;
metabolism;
Female;
Humans;
Inhibitory Concentration 50;
Lysine;
pharmacology;
NF-kappa B;
metabolism;
RNA, Messenger;
metabolism;
Receptor, ErbB-2;
genetics;
metabolism;
Signal Transduction;
Tumor Suppressor Protein p53;
metabolism
- From:
Acta Pharmaceutica Sinica
2008;43(11):1099-1105
- CountryChina
- Language:Chinese
-
Abstract:
This study is to investigate the effect of rhein lysinate on inducing human breast cancer cell line SK-Br-3 apoptosis and the role of HER-2 signal pathway in the apoptosis. MTT assay was used to detect SK-Br-3 cell proliferation. Cell cycle and apoptosis were analyzed by flow cytometry. The protein expression and the protein phosphorylation of HER-2 signal pathway were detected by Western blotting. The level of HER-2 mRNA was detected by RT-PCR and the level of HER-2 expression was also detected by immunofluorescence cytochemical methods. The results showed that rhein lysinate remarkably inhibited breast cancer SK-Br-3 cell proliferation. The IC50 value for 48 h treatment was 85 micromol x L(-1). Apoptosis in SK-Br-3 cells was induced by rhein lysinate in a dose dependent manner. The protein expressions of HER-2, NF-KB, and the protein phosphorylation of HER-2 were downregulated, however the protein expression of p53 and p21 was upregulated after rhein lysinate treatment. The level of HER-2 mRNA decreased by using RT-PCR assay and the level of HER-2 expression was also decreased by using immunofluorescence cytochemical assay after rhein lysinate treatment. It can be concluded that rhein lysinate could inhibit SK-Br-3 cell proliferation and induce apoptosis. HER-2/NF-kappaB/p53/p21 signal pathway might be involved in this process. Rhein lysinate has a good prospect to be an adjuvant chemotherapeutic drug.
