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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.