Abstract
The tumor suppressor protein p53 plays an important role in the development and progression of colon cancer, and the subcellular organelle localization directly affects its function. Wogonin (5,7-dihydroxy-8-methoxyflavone), a mono-flavonoid extracted from root of Scutellaria baicalensis Georgi, possesses acceptable toxicity and has been used in colorectal cancer (CRC) chemoprevention in pre-clinical trials by oncologist. However, the underlying anti-colon cancer mechanisms of wogonin are not yet fully understood. In the present study, the effect of wogonin on the initiation and development of colitis-associated cancer through p53 nuclear translocation was explored. AOM-DSS CRC animal model and human CRC HCT-116 cell model were used to evaluate the in vivo and in vitro anti-colon cancer action of wogonin. We observed that wogonin showed a dramaticlly preventive effect on colon cancer. Our results showed that wogonin caused apoptotic cell death in human CRC HCT-116 cell through increased endoplasmic reticulum (ER) stress. Meanwhile, excessive ER stress facilitated the cytoplasmic localization of p53 through increasing phosphor-p53 at S315 and S376 sites, induced caspase-dependent apoptosis and inhibited autophagy. Furthermore, we verified the chemoprevention effect and toxicity of wogonin in vivo by utilizing an AOM-DSS colon cancer animal model. We found that wogonin not only reduced tumor multiplicity, preserved colon length to normal (6.79 ± 0.34 to 7.41 ± 0.56, P < 0.05) but also didn’t induce side effects on various organs. In conclusion, these results explain the anti-tumor effect of wogonin in CRC and suggest wogonin as a potential therapeutic candidate for the therapeutic strategy in CRC treatment.
Highlights
Colorectal cancer is the third most commonly prevalent malignancy worldwide and the fourth cause of cancer-related death (Das et al, 2016)
Human colon cancer HCT116 cells were treated by wogonin at various concentrations (1– 100 μM) for 72 h and analyzed by MTT assay
Our results suggest that wogonin inhibits the colon cancer HCT-116 cell viability and proliferation
Summary
Colorectal cancer is the third most commonly prevalent malignancy worldwide and the fourth cause of cancer-related death (Das et al, 2016). More than 1 million new cases of CRC are reported annually and the incidence rate has been increasing. In 2012, nearly 10% of the total worldwide cancers, 1,361,000 new cases were reported and nearly half died from CRC (Siegel et al, 2017). The 5-year relative survival rate of CRC is on the rise, but the total death toll is still very high. 5-fluorouracil (5-FU), leucovorin, oxaliplatin (FOLFOX) are conventional chemotherapy regimens, often fail to eradicate advanced CRC (Neska et al, 2016). It will be a promising approach for cancer prevention and improve overall survival by utilizing food-derived, plant-derived, or pharmaceutical interventions with broad effectiveness and tolerable side effects to inhibit tumorigenesis and development
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