Identification of common or distinct genes related to antitumor activities of a medicinal herb and its major component by oligonucleotide microarray.
Although the physiological actions of many herbs are gradually being elucidated at the molecular level, it remains unclear how individual components of herbs contribute to their biological activities. In the present study, the antiproliferative activity of Coptidis rhizoma, a medicinal herb, and the major component berberine was investigated in 8 human pancreatic cancer cell lines. Gene expression patterns associated with sensitivities to each agent were analyzed with oligonucleotide arrays that comprised approximately 11,000 genes. We used a tetrazolium dye (MTT) assay to determine ID(50) values after the 8 cell lines were exposed to the 2 agents for 72 hr. The ID(50) value for berberine was correlated positively with that for C. rhizoma (r=0.725, p=0.0401). C. rhizoma killed tumor cells more effectively than purified berberine when normalized to the level of berberine present in the herb. From the oligonucleotide array data, we selected 20 and 13 genes with strong correlations (r(2)>0.81) to ID(50) values for berberine and C. rhizoma, respectively. Among these 33 genes, the levels of expression of 12 were correlated with the ID(50) values of both agents, suggesting that these genes are associated with tumor-killing activity of berberine in C. rhizoma. Expression of the remaining 21 genes was correlated with the ID(50) value of either purified berberine or C. rhizoma. Thus, we identified common and distinct genes responsible for anti-proliferative activities of purified berberine and C. rhizoma. This strategy may improve our understanding of the actions of herbs with antitumor activities.
Iizuka
Norio
N
Department of Bioregulatory Function, Yamaguchi University School of Medicine, Yamaguchi, Japan.
Oka
Masaaki
M
Yamamoto
Kotaro
K
Tangoku
Akira
A
Miyamoto
Koji
K
Miyamoto
Takanobu
T
Uchimura
Shunji
S
Hamamoto
Yoshihiko
Y
Okita
Kiwamu
K
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001599:Berberine / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D000089042:Coptis chinensis; D017931:DNA Primers / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005434:Flow Cytometry; D005562:Formazans; D020869:Gene Expression Profiling; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D015347:RNA Probes; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013778:Tetrazolium Salts; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D017931:DNA Primers; D004365:Drugs, Chinese Herbal; D005562:Formazans; D009363:Neoplasm Proteins; D015347:RNA Probes; D013778:Tetrazolium Salts; D001599:Berberine; C079782:MTT formazan; C107393:Coptidis rhizoma extract