Anti-cancer activity of Psoralea fructus through the downregulation of cyclin D1 and CDK4 in human colorectal cancer cells.
BACKGROUND
Psoralea 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.


METHODS
Cell growth was evaluated by MTT assay. The effect of PF on cyclin D1 and CDK4 expression was evaluated by Western blot or RT-PCR.


RESULTS
PF 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 (IC50value: 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.


CONCLUSIONS
Our results suggest that PF has potential to be a candidate for the development of chemoprevention or therapeutic agents for human colorectal cancer.
Department of Medicinal Plant Resources, Andong National University, Andong, 36729, Republic of Korea.
Gwang Hun
GH
Park
Department of Medicinal Plant Resources, Andong National University, Andong, 36729, Republic of Korea.
Ji Ho
JH
Sung
Department of Medicinal Plant Resources, Andong National University, Andong, 36729, Republic of Korea.
Hun Min
HM
Song
Department of Medicinal Plant Resources, Andong National University, Andong, 36729, Republic of Korea. jjb0403@anu.ac.kr.
Jin Boo
JB
Jeong
Anticancer; CDK4; Cyclin D1; Psoralea Fructus; Psoralea corylifolia
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