Planta Med 2011; 77(10): 1005-1012
DOI: 10.1055/s-0030-1270732
Biological and Pharmacological Activity
Original Papers
© Georg Thieme Verlag KG Stuttgart · New York

Involvement of Mitochondrial Permeability Transition Pore Opening in 7-Xylosyl-10-Deacetylpaclitaxel-Induced Apoptosis

Shougang Jiang1 , 2 , Yuangang Zu1 , 2 , Zhuo Wang1 , 2 , Yu Zhang1 , 2 , Yuejie Fu1 , 2
  • 1Key Laboratory of Foresty Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin, People's Republic of China
  • 2Engineering Research Center of Forest Bio-preparation, Ministry of Education, Northeast Forestry University, Harbin, People's Republic of China
Further Information

Publication History

received Sep. 30, 2010 revised January 3, 2011

accepted January 12, 2011

Publication Date:
03 February 2011 (online)

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Abstract

7-Xylosyl-10-deacetylpaclitaxel is a natural hydrophilic paclitaxel derivative. It has long been used in Chinese clinics to treat cancer. In order to further explore the underlying intracellular target of 7-xylosyl-10-deacetylpaclitaxel towards the PC-3 cell line, the ultra-structural morphology of mitochondria, the intracellular Ca2+, the intracellular ATP, the intracellular hydrogen peroxide and pro-apoptotic Bax and Bcl-2 protein expression were measured. Additionally, the changes of mitochondrial morphology and membrane potential (ΔΨm) were analyzed by atomic force microscopy (AFM) and flow cytometry, respectively. Our results suggest that the intracellular target of 7-xylosyl-10-deacetylpaclitaxel may be the mitochondrial permeability transition pore (mPTP). To further evaluate this hypothesis, we assessed the effect of a specific mPTP inhibitor (cyclosporine A) on the toxic action of 7-xylosyl-10-deacetylpaclitaxel. The 7-xylosyl-10-deacetylpaclitaxel-induced decrease in mitochondrial inner transmembrane potential (ΔΨm) was abolished by the addition of cyclosporine A (CsA) in PC-3 cells, indicating that 7-xylosyl-10-deacetylpaclitaxel may target mPTP. Furthermore, treatment with 7-xylosyl-10-deacetylpaclitaxel increased ROS levels in PC-3 cells. This effect was counteracted by 10 µM cyclosporine A. These data indicate that oxidative damage is involved in mPTP.

References

Yuangang Zu

Key Laboratory of Foresty Plant Ecology
Ministry of Education
Northeast Forestry University

No. 26, Hexing Street

Harbin 150040

People's Republic of China

Phone: +86 4 51 82 19 15 17

Fax: +86 4 51 82 10 20 82

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