Cantharidin and norcantharidin inhibit the ability of MCF-7 cells to adhere to platelets via protein kinase C pathway-dependent downregulation of α2 integrin

Shou,Liu-Mei; Zhang,Qiong-Yan; Li,Wei; Xie,Xin; Chen,Kai; Lian,Lian; Li,Zhen-Yu; Gong,Fei-Ran; Dai,Ke-Sheng; Mao,Yi-Xiang; Tao,Min

doi:10.3892/or.2013.2601

September 2013 Volume 30 Issue 3

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September 2013 Volume 30 Issue 3

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Article Open Access

Cantharidin and norcantharidin inhibit the ability of MCF-7 cells to adhere to platelets via protein kinase C pathway-dependent downregulation of α2 integrin

Authors:
- Liu-Mei Shou
- Qiong-Yan Zhang
- Wei Li
- Xin Xie
- Kai Chen
- Lian Lian
- Zhen-Yu Li
- Fei-Ran Gong
- Ke-Sheng Dai
- Yi-Xiang Mao
- Min Tao
View Affiliations / Copyright

Affiliations: Department of Oncology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China, Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40536, USA, Department of Hematology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China

Copyright: © Shou et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
Pages: 1059-1066
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Published online on: July 8, 2013

https://doi.org/10.3892/or.2013.2601
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Abstract

Cancer metastasis is a highly coordinated and dynamic multistep process in which cancer cells interact with a variety of host cells. Morphological studies have documented the association of circulating tumor cells with host platelets, where a surface coating of platelets protects tumor cells from mechanical trauma and the immune system. Cantharidin is an active constituent of mylabris, a traditional Chinese medicine. Cantharidin and norcantharidin are potent protein phosphatase 2A (PP2A) inhibitors that exhibit in vitro and in vivo antitumor activity against several types of cancer, including breast cancer. We investigated whether cantharidin and norcantharidin could repress the ability of MCF-7 breast cancer cells to adhere to platelets. Using MTT, clone formation, apoptosis, adhesion and wound-healing assays, we found that cantharidin and norcantharidin induced apoptosis and repressed MCF-7 cell growth, adhesion and migration. Moreover, we developed a flow cytometry-based analysis of tumor cell adhesion to platelets. We proved that cantharidin and norcantharidin repressed MCF-7 cell adhesion to platelets through downregulation of α2 integrin, an adhesion molecule present on the surface of cancer cells. The repression of α2 integrin expression was found to be executed through the protein kinase C pathway, the activation of which could have been due to PP2A inhibition.

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