[Rhein lysinate induces apoptosis in breast cancer SK-Br-3 cells by inhibiting HER-2 signal pathway].
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.
Lin
Ya-Jun
YJ
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Huang
Yun-Hong
YH
Zhen
Yong-Zhan
YZ
Liu
Xiu-Jun
XJ
Zhen
Yong-Su
YS
D000880:Anthraquinones / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D008239:Lysine / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000880:Anthraquinones; D000970:Antineoplastic Agents; D050759:Cyclin-Dependent Kinase Inhibitor p21; D008239:Lysine; D016328:NF-kappa B; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53; C493956:CDKN1A protein, human; C020491:rhein