1. Academic Validation
  2. Cucurbitacin D induces cell cycle arrest and apoptosis by inhibiting STAT3 and NF-κB signaling in doxorubicin-resistant human breast carcinoma (MCF7/ADR) cells

Cucurbitacin D induces cell cycle arrest and apoptosis by inhibiting STAT3 and NF-κB signaling in doxorubicin-resistant human breast carcinoma (MCF7/ADR) cells

  • Mol Cell Biochem. 2015 Nov;409(1-2):33-43. doi: 10.1007/s11010-015-2509-9.
Jin Mo Ku 1 Soon Re Kim 1 Se Hyang Hong 1 Han-Seok Choi 1 Hye Sook Seo 1 Yong Cheol Shin 1 Seong-Gyu Ko 2
Affiliations

Affiliations

  • 1 Laboratory of Clinical Biology and Pharmacogenomics, Department of Preventive Medicine, College of Oriental Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea.
  • 2 Laboratory of Clinical Biology and Pharmacogenomics, Department of Preventive Medicine, College of Oriental Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea. epiko@khu.ac.kr.
Abstract

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 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 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.

Keywords

Breast cancer; Cucurbitacin D; Doxorubicin; MCF7 cell; MCF7/ADR cell; Multidrug resistance.

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