Fisetin Inhibits Trypsin Activity and Suppresses the Growth of Colorectal Cancer in Vitro and in Vivo

Abstract

Colorectal cancer (CRC) is a malignant tumor with high incidence and bad prognosis. Therapies, which are more safe and effective, are urgently needed. Trypsin is proved to be crucial to cancer proliferation and migration, therefore, it is possible to control cancers by modulating its activity. Fisetin is a flavone with trypsin inhibition properties that was screened from more than 45 compounds derived from traditional Chinese medicine (TCM). However, the effects and mechanisms of fisetin on CRC have not been well investigated. In this study, we evaluated the effects of fisetin on 2 different CRC cell lines. Fisetin remarkably inhibited CRC cell proliferation and migration, as well as induced cell apoptosis and Go/G1 phase arrest in a dose-dependent manner. Mechanistic studies revealed that these effects were mediated partially through signaling pathways involving cell cycle regulators p21, p27, cyclinD1, and NF kappa B (NF-κB) p65. Administration of fisetin also significantly suppressed the tumor growth in tumor-bearing NOD/Shi-scid-IL2R gamma (null) (NOG) mice that had been inoculated with human HCT116 cells. Fisetin at the given dosage did not induce significant acute or chronic toxicity in rats. These data provide a potential therapeutic strategy for CRC.

Phenolic Phytochemicals for Prevention and Treatment of Colorectal Cancer: A Critical Evaluation of In Vivo Studies

“…Fisetin suppressed HCT116 induced tumor growth in NOD/Shi-scid-IL2R gamma (null) (NOG) mice in a dose-dependent manner compared to control group [218]. Another study showed that due to poor water solubility, the fisetin micelles, composed of poly(ethylene glycol)-poly(ε-caprolactone), i.e., MPEG-PCL, are more efficient antitumor agents over free fisetin as tested in CT-26 tumor model.…”

Fisetin's Promising Antitumor Effects: Uncovering Mechanisms and Targeting for Future Therapies

“…51 Li et al conducted both in vitro and in vivo experiments and found that fisetin remarkably inhibited colorectal cancer cell proliferation and migration, induced cell cycle arrest and apoptosis, and suppressed tumor growth in tumor-bearing mice. 52 Additionally, Jia et al investigated the in vivo antitumor effect of fisetin in a pancreatic cancer model and identified the enhancement of the AMPK/mTOR signaling pathway after fisetin treatment. 53 Li et al explored the effects of fisetin in a metastatic breast cancer xenograft model and observed significant inhibition of primary tumor growth and reduction in lung metastasis.…”

“… 51 Li et al conducted both in vitro and in vivo experiments and found that fisetin remarkably inhibited colorectal cancer cell proliferation and migration, induced cell cycle arrest and apoptosis, and suppressed tumor growth in tumor-bearing mice. 52 …”

“…We provided the appropriate references for the studies mentioned to ensure the scientific validity and credibility of our findings. 50 51 52 53 54 …”