Abstract
Malignant melanoma (MM) is one of the malignant tumors with highly metastatic and aggressive biological actions. Schizandrin A (SchA) is a bioactive lignin compound with strong anti-oxidant and anti-aging properties, which is stable at room temperature and is often stored in a cool dry place. Hence, we investigated the effects of SchA on MM cell line A375 and its underlying mechanism. A375 cells were used to construct an in vitro MM cell model. Cell viability, proliferation, apoptosis, and migration were detected by Cell Counting Kit-8, BrdU assay, flow cytometry, and transwell two-chamber assay, respectively. The cell cycle-related protein cyclin D1 and cell apoptotic proteins (Bcl-2, Bax, cleaved-caspase-3, and cleaved-caspase-9) were analyzed by western blot. Alteration of H19 expression was achieved by transfecting with pEX-H19. PI3K/AKT pathway was measured by detecting phosphorylation of PI3K and AKT. SchA significantly decreased cell viability in a dose-dependent manner. Furthermore, SchA inhibited cell proliferation and cyclin D1 expression. SchA increased cell apoptosis along with the up-regulation of pro-apoptotic proteins (cleaved-caspase-3, cleaved-caspase-9, and Bax) and the down-regulation of anti-apoptotic protein (Bcl-2). Besides, SchA decreased migration and down-regulated matrix metalloproteinases (MMP)-2 and MMP-9. SchA down-regulated lncRNA H19. Overexpression of H19 blockaded the inhibitory effects of SchA on A375 cells. SchA decreased the phosphorylation of PI3K and AKT while H19 overexpression promoted the phosphorylation of PI3K and AKT. SchA inhibited A375 cell growth, migration, and the PI3K/AKT pathway through down-regulating H19.
Highlights
Malignant melanoma (MM) is one of the malignant tumors with highly metastatic and aggressive biological actions
Due to the close relationship between cyclin D1 and cell cycle, we found that Schizandrin A (SchA) (30 mM) downregulated cyclin D1 (Po0.05, Figure 2C) and enhanced cell apoptosis (Po0.001, Figure 2D)
We detected the accumulated level of apoptotic proteins, and found that cleaved-caspase-3 (Po0.001), cleaved-caspase-9 (Po0.001), and Bax (Po0.01) were up-regulated while Bcl-2 was down-regulated (Po0.05) by SchA (30 mM) compared with control (Figure 2E and F). These findings indicate that SchA decreased cell proliferation and enhanced cell apoptosis
Summary
Malignant melanoma (MM) is one of the malignant tumors with highly metastatic and aggressive biological actions. MM accounted for 60–80% of skincancer related deaths [1]. Recent studies have indicated that MM is not a single entity but a set of various kinds of neoplasms with different causes, biological behaviors, and outcomes [2]. Despite the development of technology and medicine, the survival rate for advanced MM has not improved significantly in the past eight years [3]. New medicines or therapies are urgently needed to treat MM. More attention has been given to traditional Chinese medicine for novel potential treatment
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