Content area
Full Text
Introduction
Colorectal cancer is the third leading cause of mortality in the Western world (1) and has emerged as a common malignancy in the Asian population as a result of changes in diet and physical activity levels (2). Dietary habits have been related to the risk of colorectal cancer (3,4). Surgery and chemotherapy are the primary treatments for colorectal cancer. Radiotherapy is a typical adjuvant treatment after surgery or chemotherapy for high-stage colorectal cancers (5,6). However, colorectal carcinomas display a wide range of radiosensitivity (7,8). Therefore, new approaches are necessary to enhance the efficacy of radiation treatments for colorectal cancers.
Previous epidemiological studies have shown that the daily inclusion of fruit and vegetables in the diet decreases the risk of colon cancer (9). In addition, it has been reported that flavonoids, which are abundant in numerous plants, protect against a number of tumorigenic processes, including oxidative stress, inflammation, angiogenesis and cell invasion (10–12). Furthermore, flavonoids induce cell cycle arrest, apoptosis and radiosensitivity in cancer cells in vitro (13–15). The flavonoid fisetin (3,7,3′,4′-tetrahydroxyflavone) is a polyphenol found in numerous plants. A number of previous reports have shown that fisetin activates p53 activity, and represses the cyclooxygenase-2 and Wnt/epidermal growth factor receptor/nuclear factor-B signaling pathways in human cancer cells to promote apoptosis (14,16–18). In addition, fisetin inhibits the spindle checkpoint response that arrests cells in the radiosensitive G2/M phase (19,20). However, the in vivo effects of fisetin remain unclear. As fisetin is a natural and edible product with acceptable biosafety, the clinical potential of this compound is of particular interest and warrants further investigation.
Securin, which was originally isolated from rat pituitary tumor cells, is alternatively called the pituitary tumor transforming gene (21). Securin is a multi-functional protein that serves a number of biological roles, such as the regulation of cellular transformation, sister chromatid separation (22,23), gene transcription (24) and DNA damage repair (25,26). Notably, securin interacts with p53 and perturbs p53-mediated transcription and apoptosis in tumor cells (22). Thus, securin is regarded as an oncoprotein. The depletion of securin has been reported to sensitize human colorectal cancer cells to various types of treatment, including fisetin, butein and ionizing radiation (27–29). However, whether these effects can be repeated in vivo is unknown.
In the present study, tumor-bearing...