α-Mangostin, a natural product isolated from the pericarp of the mangosteen fruit, has been shown to inhibit the growth of tumor cells in various types of cancers. However, the underlying molecular mechanisms are largely unclear. Here, we report that α-mangostin suppressed the viability and epithelial-mesenchymal transition (EMT) of pancreatic cancer cells through inhibition of the PI3K/Akt pathway. Treatment of pancreatic cancer BxPc-3 and Panc-1 cells with α-mangostin resulted in loss of cell viability, accompanied by enhanced cell apoptosis, cell cycle arrest at G1 phase, and decrease of cyclin-D1. Moreover, Transwell and Matrigel invasion assays showed that α-mangostin significantly reduced the migration and invasion of pancreatic cancer cells. Consistent with these results, α-mangostin decreased the expression of MMP-2, MMP-9, N-cadherin, and vimentin and increased the expression of E-cadherin. Furthermore, we found that α-mangostin suppressed the activity of the PI3K/Akt pathway in pancreatic cancer cells as demonstrated by the reduction of the Akt phosphorylation by α-mangostin. Finally, α-mangostin significantly inhibited the growth of BxPc-3 tumor mouse xenografts. Our results suggest that α-mangostin may be potentially used as a novel adjuvant therapy or complementary alternative medicine for the management of pancreatic cancers.

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Calcitriol (1, 25-dihydroxyvitamin D3) is the most biologically active metabolite derived from the secosteroid hormone vitamin D. Apart from its calcium homeostatic effects, epidemiological studies have shown that reduced serum calcitriol levels are associated with an increased risk of some types of cancer. Numerous recent epidemiological and experimental studies have reported that it elicits anti-proliferative, apoptotic and differentiation effects in several malignant cell types. The inhibition of calcitriol results in reduced effects of anticancer drugs. Results from a number of clinical trials revealed that sufficient dosing and exposure to calcitriol is critical for achieving antitumor effects during intermittent regimens. This review summarizes the role of calcitriol in anticancer therapy and the progress in understanding its mechanism.

Metformin, a traditional first-line pharmacologic treatment for type 2 diabetes, has recently been shown to impart anti-cancer effects on hepatocellular carcinoma (HCC). However, the molecular mechanism of metformin on its antitumor activity is still not completely clear. The Sonic hedgehog (Shh) signaling pathway is closely associated with the initiation and progression of HCC. Therefore, the aim of the current study was to investigate the effects of metformin on the biological behavior of HCC and the underlying functional mechanism of metformin on the Shh pathway. The HCC cellular was induced in HepG2 cells by recombinant human Shh (rhShh). The effects of metformin on proliferation and metastasis were evaluated by proliferation, wound healing and invasion assays in vitro. The mRNA and protein expression levels of proteins related to the Shh pathway were measured by western blotting, quantitative PCR and immunofluorescence staining. Metformin inhibited rhShh-induced proliferation and metastasis. Furthermore, metformin decreased mRNA and protein expression of components of the Shh pathway including Shh, Ptch, Smo and Gli-1. Silencing of AMPK in the presence of metformin revealed that metformin could exert its inhibitory effect via AMPK. Our findings demonstrate that metformin can suppress the migration and invasion of HepG2 cells via AMPK-mediated inhibition of the Shh pathway.