Abstract
Litchi (Litchi chinensisSonnnerat, Sapindaceae), known as Chinese Cherry, is a subtropical fruit tree originating from southern China. Litchi seed extracts have diverse pharmacological effects, including anticancer. However, its anticancer effects and mechanisms on prostate cancer have not been determined. In this study, we used n-butyl alcohol extract of Litchi seed (NLS) to treat prostate cancer PC3, DU145, RM1 and C4-2B cells. NLS induced a significant decrease in cell viability and clonogenic growth in a dose-dependent manner. NLS induced cell apoptosis and cell cycle G1/S phase arrest by inactivating Akt signaling pathway, which were associated with activation of mitochondrial caspase-dependent apoptotic cascades, up-regulation of cyclin-dependent kinase (CDK) inhibitors p21 and p27, and inhibition of correlated cyclin/CDK network. In addition, NLS treatment significantly decreased cell migration and invasion via phenotypic inversion of EMT, correlated with increased expression of E-cadherin and β-catenin, and decreased expression of vimentin and snail, which is partially attributed to inhibiting Akt/GSK-3β signaling pathway. Finally, PC3 xenograft nude mice treated with NLS in vivo showed a significant decrease in tumor size without toxicity. These findings suggest that NLS has potential for development into a safe and potent alternative therapy for prostate cancer patients.
Highlights
Prostate cancer (PCa) is the second most frequently diagnosed cancer in men worldwide, with 1.1 million new cases occurred in 20121
The expression of Vimentin and Snail was remarkably down-regulated in the n-butyl alcohol extract of Litchi seed (NLS)-treated cells compared to control cells (Fig. 5E). These results indicated that NLS reduced migration and invasion capabilities in PCa cells via phenotypic inversion of epithelial-mesenchymal transition (EMT)
Mortality remains high in advanced PCa due to relapse after androgen deprivation therapy and chemotherapy
Summary
Prostate cancer (PCa) is the second most frequently diagnosed cancer in men worldwide, with 1.1 million new cases occurred in 20121. PCa is the most frequently diagnosed cancer and the second leading cause of cancer-related death among men[1,2,3]. Litchi pulp is mainly consumed freshly, but Litchi seed is discarded and underutilized. The decoctions of Chinese herbal formula containing Litchi seeds are used as indigenous remedy for urologic neoplasms including prostate cancer, bladder cancer and renal carcinoma[9,10]. There is no report to demonstrate the effects and mechanisms of Litchi seed extracts on PCa. Here, we investigated the effects of n-butyl alcohol extract of Litchi seed (NLS) on PCa PC3, DU145, RM1 and C4-2B cell lines and explored its potential mechanisms
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