Abstract
As an active constituent of the beetle Mylabris used in traditional Chinese medicine, cantharidin is a potent and selective inhibitor of protein phosphatase 2A (PP2A) that plays a crucial role in cell cycle progression, apoptosis, and cell fate. The role and possible mechanisms exerted by cantharidin in cell growth and metastasis of breast cancer were investigated in this study. Cantharidin was found to inhibit cell viability and clonogenic potential in a time- and dose-dependent manner. Cell cycle analysis revealed that cell percentage in G2/M phase decreased, whereas cells in S and G1 phases progressively accumulated with the increasing doses of cantharidin treatment. In a xenograft model of breast cancer, cantharidin inhibited tumor growth in a dose-dependent manner. Moreover, high doses of cantharidin treatment inhibited cell migration in wound and healing assay and downregulated protein levels of major matrix metalloproteinases (MMP)-2 and MMP-9. MDA-MB-231 cell migration and invasion were dose-dependently inhibited by cantharidin treatment. Interestingly, the members of the mitogen-activated protein kinase (MAPK) signaling family were less phosphorylated as the cantharidin dose increased. Cantharidin was hypothesized to exert its anticancer effect through the MAPK signaling pathway. The data of this study also highlighted the possibility of using PP2A as a therapeutic target for breast cancer treatment.
Highlights
Breast cancer remains a health threat for females worldwide
Primary antibodies against reduced glyceraldehyde-phosphate dehydrogenase (GAPDH), -actin, matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinases (MMP)-9 were purchased from Abcam (China)
These data suggested that cantharidin inhibited MDA-MB-231 cell growth in a dose- and time-dependent manner
Summary
Breast cancer remains a health threat for females worldwide. Multiple factors, including histone modification [2,3], hormone disorder [4], and transcription factors [5], are considered to influence the development and progression of breast cancer. Current knowledge considers breast cancer as a multistep disease that involves the coordinated interaction of multiple genes and the accumulation of multiple molecular and morphologic changes within a cell [6]. Treatment modalities have progressed over the last decades; the prognosis of breast cancer patients is still poor. A novel therapeutic strategy for treating breast cancer is urgently needed
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