The extract of huanglian, a medicinal herb, induces cell growth arrest and apoptosis by upregulation of interferon-beta and TNF-alpha in human breast cancer cells.
Huanglian (Coptidis rhizoma), a widely used herb in traditional Chinese medicine, has been shown recently to possess anticancer activities. However, the molecular mechanism underlying the anticancer effect of the herb is poorly understood. Specifically, whether huanglian extract affects the expression of cancer-related genes has not been defined. This study used DNA microarray technology to examine the effect of the herbal extract on expression of the common genes involved in carcinogenesis in two human breast cancer cell lines, the ER-positive MCF-7 and ER-negative MDA-MB-231 cells. Treatment of the cancer cells with huanglian extract markedly inhibited their proliferation in a dose- and time-dependent manner. The growth inhibitory effect was much more profound in MCF-7 cell line than that in MDA-MB-231 cells. DNA microarray assay revealed that treatment with huanglian dramatically increased the mRNA expression of interferon-beta (IFN-beta) and tumor necrosis factor-alpha in MCF-7 cells. Quantitative analysis by real-time PCR or western blotting confirmed the upregulation of the two genes (especially IFN-beta) in MCF-7 cells, but not in MDA-MB-231 cells. Addition of neutralizing antibody against IFN-beta to culture medium markedly inhibited the huanglian-induced antiproliferative effect, confirming the involvement of IFN-beta in the huanglian's effect and also suggesting an autocrine pathway for the action of IFN-beta in this setting. Given that IFN-beta is among the most important anticancer cytokines, the upregulation of this gene by huanglian is, at least in part, responsible for its antiproliferative effect. The results of this study implicate huanglian as a promising herb for chemoprevention and chemotherapy of certain cancers.
Kang
Jing X
JX
Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. kang.jing@mgh.harvard.edu
Liu
Jing
J
Wang
Jingdong
J
He
Chengwei
C
Li
Frederick P
FP
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D029001:Herbal Medicine; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010936:Plant Extracts / Q000494:pharmacology*; D011960:Receptors, Estrogen; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015854:Up-Regulation
D004365:Drugs, Chinese Herbal; D007370:Interferon Type I; D010936:Plant Extracts; D011960:Receptors, Estrogen; D014409:Tumor Necrosis Factor-alpha; C494417:huanglian