2. Academic Validation
  3. Alisol F 24 Acetate Enhances Chemosensitivity and Apoptosis of MCF-7/DOX Cells by Inhibiting P-Glycoprotein-Mediated Drug Efflux

Alisol F 24 Acetate Enhances Chemosensitivity and Apoptosis of MCF-7/DOX Cells by Inhibiting P-Glycoprotein-Mediated Drug Efflux

  • Molecules. 2016 Feb 4;21(2):183. doi: 10.3390/molecules21020183.
Guixiang Pan 1,  Tingting Li 2 3,  Qingqing Zeng 4 5,  Xiaoming Wang 6,  Yan Zhu 7
Affiliations

Affiliations

  • 1 Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China. guixiangp@163.com.
  • 2 Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China. litingting2559@163.com.
  • 3 Tianjin International Joint Academy of Biomedicine, Tianjin 300457, China. litingting2559@163.com.
  • 4 Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China. zengqing20080629@126.com.
  • 5 Tianjin International Joint Academy of Biomedicine, Tianjin 300457, China. zengqing20080629@126.com.
  • 6 Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China. xiaoming_w@yeah.net.
  • 7 Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China. yanzhu.harvard@icloud.com.
PMID: 26861264 DOI: 10.3390/molecules21020183
Abstract

Multidrug resistance (MDR) is a prime reason for numerous failed oncotherapy approaches. In the present study, we investigated whether Alisol F 24 acetate (ALI) could reverse the MDR of MCF-7/DOX cells, a multidrug-resistant human breast Cancer cell line. We found that ALI was a potent P-glycoprotein (P-gp) inhibitor, in the Caco-2-monolayer cell model. ALI showed a significant and concentration-dependent cytotoxic effect on MCF-7/DOX cells in combination with doxorubicin by increasing intracellular accumulation and inducing nuclear migration of doxorubicin. However, ALI had no such effect on MCF-7 cells. In addition, ALI also promoted doxorubicin-induced early Apoptosis of MCF-7/DOX cells in a time-dependent manner. These results suggest that ALI can enhance chemosensitivity of doxorubicin and reinforce its anti-cancer effect by increasing its uptake, especially inducing its nuclear accumulation in MCF-7/DOX cells. Therefore, ALI could be developed as a potential MDR-reversing agent in Cancer chemotherapy in further study.

Keywords

P-glycoprotein (P-gp); alisol F 24-acetate (ALI); doxorubicin; multidrug resistance (MDR).

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