TY - JOUR AB - Targeted therapy with reduced side effects is a major goal in cancer research. We investigated the effects of JS-K, a nitric oxide (NO) prodrug designed to release high levels of NO when suitably activated, on human breast cancer cell lines, on non-transformed human MCF-10A mammary cells, and on normal human mammary epithelial cells (HMECs). Cell viability assay, flow cytometry, electron microscopy, and Western blot analysis were used to study the effects of JS-K on breast cancer and on mammary epithelial cells. After a 3-day incubation, the IC50s of JS-K against the breast cancer cells ranged from 0.8 to 3 µM. However, JS-K decreased the viability of the MCF-10A cells by only 20% at 10-µM concentration, and HMECs were unaffected by 10 µM JS-K. Flow cytometry indicated that JS-K increased the percentages of breast cancer cells under-going apoptosis. Interestingly, flow cytometry indicated that JS-K increased acidic vesicle organelle formation in breast cancer cells, suggesting that JS-K induced autophagy in breast cancer cells. Electron microscopy confirmed that JS-K-treated breast cancer cells underwent autophagic cell death. Western blot analysis showed that JS-K induced the expression of microtubule light chain 3-II, another autophagy marker, in breast cancer cells. However, JS-K did not induce apoptosis or autophagy in normal human mammary epithelial cells. These data indicate that JS-K selectively induces programmed cell death in breast cancer cells while sparing normal mammary epithelial cells under the same conditions. The selective anti-tumor activity of JS-K warrants its further investigation in breast tumors. AD - Department of Experimental Therapeutics, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA null Division of Hematology __AMB__ Oncology, University of Florida, 2033 Mowry Road, P.O. Box 103633, Gainesville, FL 32610-3633, USA AU - McMurtry,Vanity AU - Saavedra,Joseph ,E. AU - Nieves-Alicea,René AU - Simeone,Ann-Marie AU - Keefer,Larry ,K. AU - Tari,Ana,M. DA - 2011/04/01 DO - 10.3892/ijo.2011.925 EP - 971 IS - 4 JO - Int J Oncol KW - JS-K apoptosis autophagy breast cancer nitric oxide PY - 2011 SN - 1019-6439 1791-2423 SP - 963 ST - JS-K, a nitric oxide-releasing prodrug, induces breast cancer cell death while sparing normal mammary epithelial cells T2 - International Journal of Oncology TI - JS-K, a nitric oxide-releasing prodrug, induces breast cancer cell death while sparing normal mammary epithelial cells UR - https://doi.org/10.3892/ijo.2011.925 VL - 38 ER -