CT26.WT[CT26WT]

Antiproliferative Activity of Compounds 4, 5, 6, and 7 on CT26WT Cells

Colorectal cancer (CRC) is one of the most-deadly malignancies globally. Although, when resectable, surgery may offer patients prolonged survival, chemotherapy plays an important role in the management of metastatic CRC. Anticancer drugs currently in clinical use lack selectivity and are affected by cancerous mutations, therefore new chemotherapeutic molecules are urgently needed. Pacheco et al. report the synthesis, characterization, and antiproliferative activity of a series of four steroidal carbamates, in mouse colon carcinoma CT26WT cells.

The cytotoxicity of compounds 4, 5, 6 and 7, was determined in CT26WT cells by visualizing alterations in the cell morphology and by MTT reduction, to quantitate the antiproliferative effect after 24 h of incubation with the drugs. As can be seen in Fig. 1, all steroids inhibited the growth of CT26WT cells in a dose-dependent manner and were statistically different from untreated cells. The initial inhibitory concentrations of compounds 4, 5, 6 and 7 were found to be 25 μM, 12 μM, 6 μM and 50 μM, respectively (Fig. 1A-D). At a concentration of 25 μM, the inhibitory activity order was: 7 < 4 = 5 < 6. The most active compound (6) presented an IC₅₀ of 26.8 μM, which is in accordance with the literature-reported values for steroidal carbamates. Morphologically, the number of shrunken, rounded and detached cells was higher when incubated with increasing concentrations of 4-7 compounds and not present in control cells (Fig. 1Ea, b).