Abstract
BackgroundPsoralea Fructus (PF), the dried and ripe fruit of Psoralea corylifolia exhibits an anti-cancer activity. However, the molecular mechanisms by which PF inhibits the proliferation of cancer cells have not been elucidated in detail. Cyclin D1 and CDK4 are important regulatory proteins in cell growth and are overexpressed in many cancer cells. In this study, we investigated the molecular mechanism of PF on the downregulation of cyclin D1 and CDK4 level.MethodsCell growth was evaluated by MTT assay. The effect of PF on cyclin D1 and CDK4 expression was evaluated by Western blot or RT-PCR.ResultsPF suppressed the proliferation of human colorectal cancer cell lines such as HCT116 (IC50: 45.3 ± 1.2 μg/ml), SW480 (IC50: 37.9 ± 1.6 μg/ml), LoVo (IC50: 23.3 ± 1.9 μg/ml μg/ml) HT-29 (IC50 value: 40.7 ± 1.5 μg/ml). PF induced decrease in the protein expression of cyclin D1 and CDK4. However, the mRNA expression of cyclin D1 and CDK4 did not be changed by PF; rather it suppressed the expression of cyclin D1 and CDK4 via the proteasomal degradation. In cyclin D1 degradation, we found that T286 of cyclin D1 play a pivotal role in PF-mediated cyclin D1 degradation. Subsequent experiments with several kinase inhibitors suggest that PF-mediated degradation of cyclin D1 and CDK4 is dependent on ERK1/2 and/or GSK3β.ConclusionsOur results suggest that PF has potential to be a candidate for the development of chemoprevention or therapeutic agents for human colorectal cancer.
Highlights
Psoralea Fructus (PF), the dried and ripe fruit of Psoralea corylifolia exhibits an anti-cancer activity
PF inhibits cell proliferation, and decreases the expression of cyclin D1 and CDK4 To evaluate whether PF affects the proliferation of human colorectal cancer cells, MTT assay was performed
Since cell growth inhibition is related to cell cycle arrest, we investigated the expression of cyclin D1 and CDK4 involved in cell cycle progression
Summary
Psoralea Fructus (PF), the dried and ripe fruit of Psoralea corylifolia exhibits an anti-cancer activity. Psoralea Fructus (PF), the dried and ripe fruit of Psoralea corylifolia known as “Bo-Gol-Zhee” in Korea has been used as traditional medicine in Asian [2]. Many active components have been identified in PF, and most of them belong to coumarins (psoralen, isopsoralen, and psoralidin) and flavonoids (bavachin, isobavachalcone and neobavaisoflavone) [6]. Overexpression of cyclin D1 found in various cancer cells is associated with the poor prognosis of tumor and metastasis [9].
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