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10.1007/s11010-015-2509-9

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suck abstract from ncbi


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pmid26169986
      Mol+Cell+Biochem 2015 ; 409 (1-2 ): 33-43
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  • Cucurbitacin D induces cell cycle arrest and apoptosis by inhibiting STAT3 and NF-?B signaling in doxorubicin-resistant human breast carcinoma (MCF7/ADR) cells #MMPMID26169986
  • Ku JM ; Kim SR ; Hong SH ; Choi HS ; Seo HS ; Shin YC ; Ko SG
  • Mol Cell Biochem 2015[Nov]; 409 (1-2 ): 33-43 PMID26169986 show ga
  • 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-?B, I?B, and caspases were measured by Western blot analysis. Nuclear staining of Stat3 and NF-?B was measured by immunocytochemistry. STAT3 and NF-?B transcriptional activity was detected by STAT3 and NF-?B 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 24 h. 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 I?B? level in the cytosol and a decrease in the p-NF-?B level in the nucleus. Finally, cucurbitacin D inhibited translocation of Stat3 and NF-?B and decreased transcriptional activity in the nucleus. Cucurbitacin D decreases cell proliferation and induces apoptosis by inhibiting Stat3 and NF-?B signaling in doxorubicin-resistant breast cancer cells. Cucurbitacin D could be used as a useful compound to treat adriamycin-resistant patients.
  • |Apoptosis/*drug effects [MESH]
  • |Breast Neoplasms/*drug therapy/pathology [MESH]
  • |Caspases/metabolism [MESH]
  • |Cell Line, Tumor [MESH]
  • |Cell Proliferation/drug effects [MESH]
  • |Cell Survival/drug effects [MESH]
  • |Doxorubicin/*pharmacology [MESH]
  • |Drug Resistance, Multiple [MESH]
  • |Drug Resistance, Neoplasm [MESH]
  • |Female [MESH]
  • |G2 Phase Cell Cycle Checkpoints/*drug effects [MESH]
  • |Gene Expression Regulation, Neoplastic/drug effects [MESH]
  • |Humans [MESH]
  • |I-kappa B Proteins/metabolism [MESH]
  • |MCF-7 Cells [MESH]
  • |NF-KappaB Inhibitor alpha [MESH]
  • |NF-kappa B/*antagonists & inhibitors/metabolism [MESH]
  • |STAT3 Transcription Factor/*antagonists & inhibitors/metabolism [MESH]
  • |Signal Transduction/drug effects [MESH]


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