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

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

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

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.

Original languageEnglish
Pages (from-to)1059-1066
Number of pages8
JournalOncology Reports
Volume30
Issue number3
DOIs
StatePublished - Sep 2013

Keywords

  • Breast cancer
  • Cantharidin and norcantharidin
  • Integrin α2
  • Platelet
  • Protein kinase C
  • Protein phosphatase 2A

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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