SHetA2 and its Analogs Induce Growth Inhibition in Human Glioblastoma Cells

SHetA2, a flexible heteroarotinoid and new cancer‐preventative drug candidate, has exhibited growth inhibition in many human cancer cell lines such as lung, kidney, ovarian, and colon and in animal models of cancer. Because SHetA2 has high lipophilicity (Log P of 7.09), indicating low bioavailability, this suggests that SHetA2 is not an ideal drug candidate (Ideal Log P between 0 and 5). In order to address this issue, modifications were done to the thiochroman ring, resulting in SL‐analogs with lower Log P values. In this study, we examined the growth inhibitory effects of SHetA2 and three thiochroman analogs, SL‐01‐39, SL‐01‐30, and SL‐01‐18 on T98‐G cells, a human glioblastoma cell line. After T98‐G cells were treated for 48 hours with SHetA2 and its analogs at 0.5, 1, 5, 10, and 20 μM, MTS assays were performed to measure cell proliferation and calculate their GI 50 values (drug concentration which causes 50% inhibition of cell growth). In addition, trypan blue exclusion assays were performed, using a Vi‐Cell XR cell counter, to determine percent cell viability and relative cell counts of T98‐G cells after treatment with SHetA2 or its analogs. GraphPad Prism statistical software was used to generate a non‐linear regression model from the MTS assay readings to calculate the GI 50 values. Results from trypan blue exclusion were analyzed, using Microsoft Excel, to determine the trend in cell viability and viable cell counts with respect to drug concentrations. GI 50 values of SHetA2, SL‐01‐39, SL‐01‐30, and SL‐01‐18 were calculated to be 5.57 μM, 5.38 μM, 6.41 μM, and 5.31 μM, respectively, using a one‐phase decay model. With trypan blue exclusion assay, percent cell viability remained relatively unaffected in T98‐G cells treated with SHetA2 and its analogs, despite increasing concentrations. On the contrary, trypan blue exclusion assay results showed a significant decrease in relative cell counts in cells treated with SHetA2 or its analogs when compared to the untreated cells. This is the first report showing the growth inhibitory effects of SHetA2 in T98‐G human glioblastoma cells. The GI 50 value of SHetA2 in T98‐G cells is in low micromolar range (~5 μM), comparable to its GI 50 values in other cell lines published in literature. In addition, the GI 50 values of the three analogs, SL‐01‐39, SL‐01‐30, and SL‐01‐18, were comparable to that of SHetA2. SHetA2 and its analogs decreased the relative cell number of T98‐G cells without significantly affecting cell viability, suggesting that these agents primarily inhibit cell growth of T98‐G cells without inducing cytotoxic effects. Further investigation on the mechanism of growth inhibition is ongoing. Support or Funding Information Touro CA COP‐MS Program for funding this research. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .