Cancer stem cells (CSCs) are notoriously drug resistant and are well known for their ability to undergo self-renewal and differentiation into more mature cancer cells. To date, there has been a notable dearth of investigations regarding the exact role and functions of isolated populations of CSCs., In addition, the prevalence of CSCs in malignancy is still a matter of some debate and controversy. In this research, the aim was to identify specific CSC markers and to isolate the CSC subpopulations from colon cancers for study into ways of rendering them more susceptible to chemotherapythe aims also included to examine the colorectal CSCs and identify drugs targeting purified CSCs in culture as well as in pre-clinical CRC models as a means of eliminating this type of cancer cell. This study developed a method for selectively enriching CSC populations to establish a basis for testing the effects of drugs on cancer metastasis. SW480 and CT26 parental wild-type (WT) cells were transfected with a vector encoding the octamer-binding transcription factor 4 (OCT4) promoter site regulating expression of enhanced green fluorescent protein (GFP). The most highly positive OCT4-GFP cell population after extensive rounds of sorting (the top ~1%–5%) could be further enriched by intermittent cycling involving alternating conditions of growth (between normoxia and anoxia). The highly enriched CT26 OCT4-GFPCSC population produced significantly greater tumour numbers with larger tumour sizes than did the CT26 WT inoculated mice. However, colorectal tumours formed by either cell types were significantly decreased (~50%) in numbers and volumes by celecoxib treatment. Significant levels of red blood cells were present in the peritoneal cavities of mice with the untreated colorectal tumours but greatly inhibited peritoneal angiogenesis was noted in the celecoxib-treated mice. Using these model systems for study will ensure that the role of CSC-enriched populations in tumour growth and metastasis and their therapeutic targeting can now be effectively conducted. The evidence obtained here also supports the potential for celecoxib to be repurposed and used in chemosensitising colorectal cancer cells, thereby rendering them more susceptible to standard chemotherapies such as doxorubicin and 5-fluorouracil.