title: Cantharidin and norcantharidin inhibit the ability of MCF-7 cells to adhere to platelets via protein kinase C pathway-dependent downregulation of α2 integrin.
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.
authors.affiliation: Department of Oncology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Liu-Mei
authors.initials: LM
authors.lastname: Shou
authors.forename: Qiong-Yan
authors.initials: QY
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Xin
authors.initials: X
authors.lastname: Xie
authors.forename: Kai
authors.initials: K
authors.lastname: Chen
authors.forename: Lian
authors.initials: L
authors.lastname: Lian
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Li
authors.forename: Fei-Ran
authors.initials: FR
authors.lastname: Gong
authors.forename: Ke-Sheng
authors.initials: KS
authors.lastname: Dai
authors.forename: Yi-Xiang
authors.initials: YX
authors.lastname: Mao
authors.forename: Min
authors.initials: M
authors.lastname: Tao
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D002193:Cantharidin / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D039421:Integrin alpha2 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D061986:MCF-7 Cells; D010973:Platelet Adhesiveness / Q000187:drug effects*; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D004791:Enzyme Inhibitors; D039421:Integrin alpha2; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051996:Transcription Factor RelA; C069741:norcantharidin; D011493:Protein Kinase C; D002193:Cantharidin