title: Effect of berberine on p53 expression by TPA in breast cancer cells.
abstract: Berberine (BBR), an isoquinoline derivative alkaloid compound, has been             reported to have anti-oxidant and anti-carcinogenic effects. A loss of functional             p53 is involved with an increased risk of cancer proliferation and metastasis.             Here, we investigated the effect of BBR on the transcriptional activity and the             protein expression of p53 in p53-positive (wild- type, MCF7 cells) and p53-negative             (mutant, MDA-MB231 cells) human breast cancer cells. Our results showed that the             basal level of p53 mRNA and protein expression was increased by BBR treatment.             However, tumor promoter, TPA, decreased the level of p53 mRNA and protein expression             in MCF7 cells with wild-type p53. In addition, TPA-induced down-regulation of             p53 mRNA and protein expression was increased by UO126, but not by SP600125 and             SB203580. To verify the regulatory mechanism of p53 protein expression, we investigated             the effects of proteasomal inhibitors (ALLN and MG132) or a lysosomal inhibitor             (chloroquine) on TPA-induced down-regulation of p53. We observed that TPA-induced             down-regulation of p53 protein was prevented by ALLN and MG132, but not by chloroquine.             Further, we investigated the effect of BBR on TPA-induced down-regulation of p53             mRNA and protein levels. Interestingly, the levels of TPA-induced down-regulation             of p53 mRNA and protein were prevented by BBR, but MDA-MB231 cells with mutated             p53 were not affected. In addition, TPA-induced down-regulation of p53 mRNA was             also prevented by BBR. Taken together, we suggest that BBR may be used as an effective             ingredient for anticancer products, which trigger the transcriptional activity             and the inhibition of the degradation of p53, a tumor suppressor gene, in human             breast cancer.
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Republic of Korea.
authors.forename: Sangmin
authors.initials: S
authors.lastname: Kim
authors.forename: Jeonghun
authors.initials: J
authors.lastname: Han
authors.forename: Nam-Young
authors.initials: NY
authors.lastname: Kim
authors.forename: Se Kyung
authors.initials: SK
authors.lastname: Lee
authors.forename: Dong Hui
authors.initials: DH
authors.lastname: Cho
authors.forename: Min-Young
authors.initials: MY
authors.lastname: Choi
authors.forename: Jee Soo
authors.initials: JS
authors.lastname: Kim
authors.forename: Jung-Han
authors.initials: JH
authors.lastname: Kim
authors.forename: Jun-Ho
authors.initials: JH
authors.lastname: Choe
authors.forename: Seok Jin
authors.initials: SJ
authors.lastname: Nam
authors.forename: Jeong Eon
authors.initials: JE
authors.lastname: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001599:Berberine / Q000494:pharmacology*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D002273:Carcinogens / Q000633:toxicity; D045744:Cell Line, Tumor; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D011725:Pyridines / Q000633:toxicity; D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D002273:Carcinogens; D011725:Pyridines; D012333:RNA, Messenger; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C431843:tris(2-pyridylmethyl)amine; D001599:Berberine