Tumor Biology

, Volume 37, Issue 2, pp 1919–1931 | Cite as

Isocyclopamine, a novel synthetic derivative of cyclopamine, reverts doxorubicin resistance in MCF-7/ADR cells by increasing intracellular doxorubicin accumulation and downregulating breast cancer stem-like cells

  • Ming Liu
  • Weiyi Zhang
  • Wei Tang
  • Yanjuan Wang
  • Xingzeng Zhao
  • Xiangyun Wang
  • Xin Qi
  • Jing Li
Original Article


Cyclopamine (CPM) showed promise as a human cancer chemotherapy agent. However, limitations such as stomach acid instability and low solubility impair its clinical application. In this study, we synthesized a novel CPM analogue, isocyclopamine (ICPM), which had comparative bioactivity with CPM and improved stability and solubility. ICPM reversed doxorubicin resistance and had potent synergy with doxorubicin in MCF-7/ADR cells. We further demonstrated that the synergistic mechanism was related to the increased intracellular accumulation of doxorubicin in the cells and the downregulation of the cancer stem-like cells via modulation on both ABCB1 and ABCG2 transporters with independence of Smoothened. The present study identified ICPM as a novel derivative of CPM with better stability and solubility, which provided a useful tool for the biological and medicinal studies, as well as a novel agent for the development of new cancer chemotherapy with improved efficacy.


Cyclopamine Isocyclopamine MCF-7/ADR ABCB1 ABCG2 



This work was supported by NSFC-Shandong Joint Fund (No. U1406402), the Natural Science Foundation of China (No. 81373323), the Natural Science Foundation of Shandong Province (No. ZR2012CM005, No. ZR2015HM010), and the Young Talent Project at Ocean University of China (No. 201412007).

Conflict of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Ming Liu
    • 1
  • Weiyi Zhang
    • 1
  • Wei Tang
    • 1
  • Yanjuan Wang
    • 1
  • Xingzeng Zhao
    • 2
  • Xiangyun Wang
    • 3
  • Xin Qi
    • 1
  • Jing Li
    • 1
  1. 1.Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of ChinaQingdaoChina
  2. 2.Institute of Botany, Jiangsu Province and Chinese Academy of Sciences (Nanjing Botanical Garden, Mem. Sun Yat-sen)NanjingChina
  3. 3.Nanjing Spring & Autumn Biological Engineering Co., Ltd, ChinaNanjingChina

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