Fang Xie1, Fangyu Peng2,3,4. 1. Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, U.S.A. 2. Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, U.S.A. fangyu.peng@UTSouthwestern.edu. 3. Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, U.S.A. 4. Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, U.S.A.
Abstract
BACKGROUND/AIM: Knockdown of human copper transporter 1 has been associated with reduction in copper uptake and suppression of prostate cancer cell proliferation and tumor growth. This study evaluated the effects of steroid-based compounds on copper uptake and proliferation of prostate cancer cells based on their anticancer activity and previous docking analysis of steroid-based copper transporter 1 inhibitors. MATERIALS AND METHODS: We synthesized several new steroid-based compounds and used 64Cu uptake assay and copper quantification assay with inductively coupled plasma mass spectrometry to study their effects on the cellular copper uptake by prostate cancer cells. Additionally, we used CCK-8 cell proliferation assay to study their effects on the proliferation of prostate cancer cells. RESULTS: Significant reduction in cellular copper uptake was observed in the prostate cancer cells treated with these new steroid-based compounds. Moreover, proliferation of prostate cancer cells was suppressed by treatment with the steroid-based compound 6, which had the strongest copper uptake inhibition activity. CONCLUSION: Reduction in copper uptake and inhibition of cell proliferation were demonstrated in prostate cancer cells treated with the new steroid-based compounds synthesized in this study. Steroid-based copper transporter 1 inhibitors may become novel anticancer drugs for targeted anti-copper therapy of prostate cancer and other copper hypermetabolic cancers.
BACKGROUND/AIM: Knockdown of human copper transporter 1 has been associated with reduction in copper uptake and suppression of prostate cancer cell proliferation and tumor growth. This study evaluated the effects of steroid-based compounds on copper uptake and proliferation of prostate cancer cells based on their anticancer activity and previous docking analysis of steroid-based copper transporter 1 inhibitors. MATERIALS AND METHODS: We synthesized several new steroid-based compounds and used 64Cu uptake assay and copper quantification assay with inductively coupled plasma mass spectrometry to study their effects on the cellular copper uptake by prostate cancer cells. Additionally, we used CCK-8 cell proliferation assay to study their effects on the proliferation of prostate cancer cells. RESULTS: Significant reduction in cellular copper uptake was observed in the prostate cancer cells treated with these new steroid-based compounds. Moreover, proliferation of prostate cancer cells was suppressed by treatment with the steroid-based compound 6, which had the strongest copper uptake inhibition activity. CONCLUSION: Reduction in copper uptake and inhibition of cell proliferation were demonstrated in prostate cancer cells treated with the new steroid-based compounds synthesized in this study. Steroid-based copper transporter 1 inhibitors may become novel anticancer drugs for targeted anti-copper therapy of prostate cancer and other copper hypermetabolic cancers.