RESUMEN
Colorectal cancer is a prevalent malignant tumor with a complex and diverse pathogenesis. In recent years, natural products have shown promising application prospects as sources of anticancer drugs. BBR, a class of benzoquinoline alkaloids extracted from various plants, is widely used in disease treatments owing to its pharmacological activities, including antibacterial, anti-inflammatory, antioxidant, anticancer, and anti-angiogenesis properties. Research has demonstrated that BBR exerts an anti-Salmonella and -Escherichia coli infection effect, attenuating inflammatory reactions by inhibiting harmful bacteria. During the stage of colorectal precancerous lesions, BBR inhibits the activity of cell cyclin by regulating the PI3K/AKT, MAPK, and Wnt signaling pathways, thereby decelerating the cell cycle progression of polyp or adenoma cells. Moreover, the inhibitory effect of BBR on colorectal cancer primarily occurs through the regulation of the cancer cell cycle, anti-angiogenesis, gut microbiota, and antioxidant pathways. The specific involved pathways include the MPK/ERK, NF-kB, and EGFR signaling pathways, encompassing the regulation of Bcl-2 family proteins, vascular endothelial growth factor, and superoxide dismutase. This study reviews and summarizes, for the first time, the specific mechanisms of action of BBR in the carcinogenesis process of colorectal cancer, providing novel insights for its clinical application in intestinal diseases.
RESUMEN
BACKGROUND: Emerging evidence showed that FAT10 is a vital regulator of tumor occurrence and development. The molecular mechanisms underlying the specific role of FAT10 in colorectal cancer (CRC) are not yet known. AIMS: To investigate whether FAT10 participates in the proliferation, invasion and metastasis of CRC. METHODS: This study investigated the function and clinical significance of FAT10 protein expression in CRC. Furthermore, over-expression and knockdown experiments of FAT10 were developed to explore their effects on CRC cell migration and proliferation. Moreover, a molecular mechanism of FAT10 regulate calpain small subunit 1(Capn4) was explored. RESULTS: In this research, the FAT10 expression level was elevated in CRC tissues compared to corresponding normal tissues. In addition, the elevated FAT10 expression level is significantly linked to advanced clinical stage and poor CRC prognosis. Furthermore, a very high expression of FAT10 was observed in CRC cells, and FAT10 overexpression significantly enhanced the in vivo proliferation, invasion, and metastasis of the cells, whereas knockdown of FAT10 inhibited all these cellular factors in both in vivo and in vitro environments. Moreover, the outcomes of this study suggested that FAT10 enhances colorectal cancer progression through enhancement of Capn4 expression, leading to the progression of various human tumors, as reported by previous research. The mechanism via which FAT10 promotes CRC cells proliferation, invasion, and metastasis involves modification of the ubiquitination and degradation processes of Capn4. CONCLUSION: FAT10 is a vital regulator of the tumorigenesis and advancement of CRC, thus serving as a promising pharmaceutical target for treating CRC patients.
