caa a22 4500 606234829 CHVBK 20210128101239.0 cr unu---uuuuu 210128e20151101xx s 000 0 eng 10.1007/s11010-015-2509-9 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2509-9 Cucurbitacin D induces cell cycle arrest and apoptosis by inhibiting STAT3 and NF-κB signaling in doxorubicin-resistant human breast carcinoma (MCF7/ADR) cells [Elektronische Daten] [Jin Ku, Soon Kim, Se Hong, Han-Seok Choi, Hye Seo, Yong Shin, Seong-Gyu Ko] Breast cancer is the most common cancer for women and is a major cause of mortality in women. Doxorubicin is a generally used chemotherapy drug for breast cancer. However, multidrug resistance of breast cancer interferes with the chemotherapy. We examined whether cucurbitacin D affects doxorubicin resistance of MCF7/ADR breast cancer cells. Cell viability was measured by MTT assay. Levels of p-STAT3, p-NF-κB, IκB, and caspases were measured by Western blot analysis. Nuclear staining of Stat3 and NF-κB was measured by immunocytochemistry. STAT3 and NF-κB transcriptional activity was detected by STAT3 and NF-κB luciferase reporter gene assays. Analysis of cell cycle arrest was performed by flow cytometry. Induction of apoptosis by cucurbitacin D was measured by Annexin V-FITC/propidium iodide assay. More than 90% of MCF7/ADR cells lived upon treatment with doxorubicin for 24h. However, upon treatment with cucurbitacin D, cell death was more than 60%. Co-administration of cucurbitacin D and doxorubicin induced apoptosis, and G2/M cell cycle arrest, and inhibited upregulated Stat3 by doxorubicin on MCF7/ADR cells. Additionally, cucurbitacin D led to an increase in the IκBα level in the cytosol and a decrease in the p-NF-κB level in the nucleus. Finally, cucurbitacin D inhibited translocation of Stat3 and NF-κB and decreased transcriptional activity in the nucleus. Cucurbitacin D decreases cell proliferation and induces apoptosis by inhibiting Stat3 and NF-κB signaling in doxorubicin-resistant breast cancer cells. Cucurbitacin D could be used as a useful compound to treat adriamycin-resistant patients. The Author(s), 2015 Breast cancer nationallicence Cucurbitacin D nationallicence Doxorubicin nationallicence Multidrug resistance nationallicence MCF7 cell nationallicence MCF7/ADR cell nationallicence Ku Jin Laboratory of Clinical Biology and Pharmacogenomics, Department of Preventive Medicine, College of Oriental Medicine, Kyung Hee University, 130-701, Seoul, Republic of Korea aut Kim Soon Laboratory of Clinical Biology and Pharmacogenomics, Department of Preventive Medicine, College of Oriental Medicine, Kyung Hee University, 130-701, Seoul, Republic of Korea aut Hong Se Laboratory of Clinical Biology and Pharmacogenomics, Department of Preventive Medicine, College of Oriental Medicine, Kyung Hee University, 130-701, Seoul, Republic of Korea aut Choi Han-Seok Laboratory of Clinical Biology and Pharmacogenomics, Department of Preventive Medicine, College of Oriental Medicine, Kyung Hee University, 130-701, Seoul, Republic of Korea aut Seo Hye Laboratory of Clinical Biology and Pharmacogenomics, Department of Preventive Medicine, College of Oriental Medicine, Kyung Hee University, 130-701, Seoul, Republic of Korea aut Shin Yong Laboratory of Clinical Biology and Pharmacogenomics, Department of Preventive Medicine, College of Oriental Medicine, Kyung Hee University, 130-701, Seoul, Republic of Korea aut Ko Seong-Gyu Laboratory of Clinical Biology and Pharmacogenomics, Department of Preventive Medicine, College of Oriental Medicine, Kyung Hee University, 130-701, Seoul, Republic of Korea aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 409/1-2(2015-11-01), 33-43 0300-8177 409:1-2<33 2015 409 11010 https://doi.org/10.1007/s11010-015-2509-9 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2509-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ku Jin Laboratory of Clinical Biology and Pharmacogenomics, Department of Preventive Medicine, College of Oriental Medicine, Kyung Hee University, 130-701, Seoul, Republic of Korea aut NATIONALLICENCE 700 1- Kim Soon Laboratory of Clinical Biology and Pharmacogenomics, Department of Preventive Medicine, College of Oriental Medicine, Kyung Hee University, 130-701, Seoul, Republic of Korea aut NATIONALLICENCE 700 1- Hong Se Laboratory of Clinical Biology and Pharmacogenomics, Department of Preventive Medicine, College of Oriental Medicine, Kyung Hee University, 130-701, Seoul, Republic of Korea aut NATIONALLICENCE 700 1- Choi Han-Seok Laboratory of Clinical Biology and Pharmacogenomics, Department of Preventive Medicine, College of Oriental Medicine, Kyung Hee University, 130-701, Seoul, Republic of Korea aut NATIONALLICENCE 700 1- Seo Hye Laboratory of Clinical Biology and Pharmacogenomics, Department of Preventive Medicine, College of Oriental Medicine, Kyung Hee University, 130-701, Seoul, Republic of Korea aut NATIONALLICENCE 700 1- Shin Yong Laboratory of Clinical Biology and Pharmacogenomics, Department of Preventive Medicine, College of Oriental Medicine, Kyung Hee University, 130-701, Seoul, Republic of Korea aut NATIONALLICENCE 700 1- Ko Seong-Gyu Laboratory of Clinical Biology and Pharmacogenomics, Department of Preventive Medicine, College of Oriental Medicine, Kyung Hee University, 130-701, Seoul, Republic of Korea aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 409/1-2(2015-11-01), 33-43 0300-8177 409:1-2<33 2015 409 11010