Abstract
Cell adhesion, migration and invasion are critical steps for carcinogenesis and cancer metastasis. Ganoderma lucidum, also called Lingzhi in China, is a traditional Chinese medicine, which exhibits anti-proliferation, anti-inflammation and anti-metastasis properties. Herein, GAEE, G. lucidum extract mainly contains ganoderiol A (GA), dihydrogenated GA and GA isomer, was shown to inhibit the abilities of adhesion and migration, while have a slight influence on that of invasion in highly metastatic breast cancer MDA-MB-231 cells at non-toxic doses. Further investigation revealed that GAEE decreased the active forms of focal adhesion kinase (FAK) and disrupted the interaction between FAK and SRC, which lead to deactivating of paxillin. Moreover, GAEE treatment downregulated the expressions of RhoA, Rac1, and Cdc42, and decreased the interaction between neural Wiskott-Aldrich Syndrome protein (N-WASP) and Cdc42, which impair cell migration and actin assembly. To our knowledge, this is the first report to show that G.lucidum triterpenoids could suppress cell migration and adhesion through FAK-SRC-paxillin signaling pathway. Our study also suggests that GAEE may be a potential agent for treatment of breast cancer.
Highlights
Breast cancer is the second most common form of cancer worldwide and the leading cause of cancer death among women [1]
Cytotoxicity of GAEE in MDA-MB-231 cells The effects of GAEE (0–40 mg/ml) on cell viability was detected by MTT assay and the morphological changes were observed using phase-contrast microscopy
Hoechst-33342 staining of MDA-MB-231 showed no obvious condensation of nuclear chromatin after treated with GAEE (Fig. 2C)
Summary
Breast cancer is the second most common form of cancer worldwide and the leading cause of cancer death among women [1]. The significant improvements in preventing and diagnosis of this diseases by increasing public health education, pre-clinical screening, and targeted therapies [2,3], the mortality remains relatively high because of the recurrence and distant metastases [4,5]. The metastatic process includes the loss of cell-to-cell and cellto-basement-membrane adhesion, epithelial-mesenchymal transition, increased cell motility and invading extracellular matrix (ECM) [6]. FAK, a non-receptor protein tyrosine kinase, has been implicated in controlling integrin- and growth factor receptormediated biological processes including cell spreading, motility, migration, differentiation, angiogenesis and survival [7]. Increased FAK expression and activity are correlated with malignant or metastatic disease and poor prognosis in patients [9]
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