Brazilein, a compound isolated from Caesalpinia sappan Linn., induced growth inhibition in breast cancer cells via involvement of GSK-3β/β-Catenin/cyclin D1 pathway.
Caesalpinia sappan Linn. has long been used in traditional medicine in China. Here, the anticancer activity of brazilein, a compound isolated from C. sappan Linn. was investigated. MTT assay showed that the IC50 value of brazilein against human breast cancer MCF-7 cells was 7.23 ± 0.24 μmol/L. PI staining and flow cytometry analysis indicated that brazilein caused cell cycle arrest in G1 phase. Western blot and RT-PCR assay demonstrated that cyclin D1, a key factor of the G1 to S phase progression, was downregulated in a concentration-dependent manner by brazilein treatment. Further Western blot and RNA interference assay showed that brazilein treatment activated GSK-3β and following reduced β-Catenin protein, which accounted for the downregulation of cyclin D1 and blockage of cell cycle at G1 phase. Together, all these results illustrated that brazilein induced growth inhibition of breast cancer cells and downregulation of GSK-3β/β-Catenin pathway was involved in its action mechanism.
Department of Pathology, Guangzhou Medical University, Guangzhou 510182, China. Electronic address: sohutly@163.com.
Li-yang
LY
Tao
Jian-ying
JY
Li
Jian-ye
JY
Zhang
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001578:Benzopyrans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D029911:Caesalpinia / Q000737:chemistry*; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007192:Indenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D061986:MCF-7 Cells; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D051176:beta Catenin / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D001578:Benzopyrans; C530104:CCND1 protein, human; C495270:CTNNB1 protein, human; D007192:Indenes; D051176:beta Catenin; D019938:Cyclin D1; C050295:brazilein; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3
Brazilein; Breast cancer; Cell cycle; Cyclin D1; GSK-3β/β-Catenin pathway