Objective: We examined whether cucurbitacin D affects doxorubicin resistance of MCF7/ADR breast cancer cells.
Methods: 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 VFITC/PI assay.
Results: 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, 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.
Conclusion: 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.
Note: This abstract was not presented at the meeting.
Citation Format: Jin Mo Ku, Se Hyang Hong, Myeong-Sun Kim, Hyo In Kim, Soo-Yeon Kang, Kangwook Lee, Yu-Jeong Choi, Chunhoo Cheon, CHING WEN HUANG, Youme Ko, Yui Sasaki, Sohyeon Kang, Ji Hye Kim, Hye Sook Seo, Tai Young Kim, Yong Cheol Shin, Seong-Gyu Ko. Cucurbitacin D induces cell cycle arrest and apoptosis by inhibiting STAT3 and NF-κB signaling in doxorubicin-resistant human breast carcinoma (MCF7/ADR) cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2320. doi:10.1158/1538-7445.AM2017-2320