J Cancer Prev.  2018 Mar;23(1):10-17. 10.15430/JCP.2018.23.1.10.

Esculetin Inhibits the Survival of Human Prostate Cancer Cells by Inducing Apoptosis and Arresting the Cell Cycle

• Turkekul K
• Colpan RD
• Baykul T
• Ozdemir MD
• Erdogan S

• KMID: 2416947
• DOI: http://doi.org/10.15430/JCP.2018.23.1.10

Abstract

BACKGROUND
Prostate cancer (PCa) is one of the most important causes of death in men and thus new therapeutic approaches are needed. In this study, antiproliferative and anti-migration properties of a coumarin derivative esculetin were evaluated.
METHODS
Human PCa cell lines PC3, DU145, and LNCaP were treated with various concentrations of esculetin for 24 to 72 hours, and cell viability was determined by the MTT test. Cell cycle and apoptosis were analyzed by using cell-based cytometer. Gene expression levels were assessed by reverse transcription and quantitative real-time PCR, cell migration was determined by the wound healing assay. The protein expression was measured by Western blotting.
RESULTS
Esculetin inhibited cell proliferation in a dose- and time-dependent manner. Cell migration was inhibited by esculetin treatment. Administration of esculetin significantly reduced the cells survival, induced apoptosis and caused the G1 phase cell cycle arrest shown by image-based cytometer. The induced expression of cytochrome c, p53, p21 and p27, and down-regulated CDK2 and CDK4 may be the underlying molecular mechanisms of esculetin effect. Esculetin suppressed phosphorylation of Akt and enhanced protein expression of tumor-suppressor phosphatase and tensin homologue.
CONCLUSIONS
Our findings showed that the coumarin derivative esculetin could be used in the management of PCa. However, further in vivo research is needed.

Keyword

Esculetin; Apoptosis; Cell cycle; Prostate cancer; Cancer prevention

MeSH Terms

Apoptosis*
Blotting, Western
Cause of Death
Cell Cycle Checkpoints
Cell Cycle*
Cell Line
Cell Movement
Cell Proliferation
Cell Survival
Cytochromes c
G1 Phase
Gene Expression
Humans*
Male
Passive Cutaneous Anaphylaxis
Phosphorylation
Prostate*
Prostatic Neoplasms*
Real-Time Polymerase Chain Reaction
Reverse Transcription
Wound Healing
Cytochromes c