Colorectal cancer is the third most frequently diagnosed cancer, and the second most common cause of cancer-related deaths worldwide [1]. Many chemotherapy drugs are used to treat this cancer, but in many cases the effectiveness of the drug treatment is impaired by the tumour’s innate or acquired resistance to chemotherapy treatment. Innate resistance can be caused by tumour heterogeneity, where the tumour is composed of sub-populations with different sensitivities, which makes eradication of the cancer extremely difficult.
To investigate the heterogeneity of DLD-1 human colorectal cancer cells, this cell line was cloned by seeding the cells one at a time in separate plates and waiting for the formation of separate clonal populations. From the 26 clones produced, those with a different sensitivity to chemotherapeutic drugs oxaliplatin and cisplatin compared to the parental line were selected. The viability of the parental DLD-1 line and its clones K, M, Z, X, K after exposure to the ferroptosis inducer RSL3 was further investigated using flow cytometry. RSL3 was chosen for the heterogeneity assay because resistant tumour cells may be sensitive to a newly discovered type of cell death – ferroptosis [2]. This form of death is characterized by an iron-dependent accumulation of reactive oxygen species (ROS) in the cell [3]. The results showed an increased resistance of clone K and sensitivity of clone Z to RSL3 treatment, compared to the parental line.
In conclusion, our results indicate that subpopulations of colorectal cancer cells DLD-1 have different sensitivity to ferroptosis inducer RSL3.