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Honokiol, an active compound of Magnolia officinalis, exerted many anticancer effects on various types of cancer cells. We explored its effects on the elimination of cancer stem-like side population (SP) cells in human oral squamous cell carcinoma SAS cells. The sorted SP cells possessed much higher expression of sternness genes, such as ABCG2, ABCC5, EpCAM, OCT-4, CD133, CD44, and β-catenin, and more clonogenicity as compared with the Non-SP cells. After 48 h of treatment, honokiol dose dependently reduced the proportion of SP from 2.53% to 0.09%. Apoptosis of honokiol-treated SP cells was evidenced by increased annexin V staining and cleaved caspase-3 as well as decreased Survivin and Bcl-2. Mechanistically, honokiol inhibited the CD44 and Wnt/β-catenin signaling of SP cells. The Wnt signaling transducers such as β-catenin and TCF-4 were decreased in honokiol-treated SP cells, while the β-catenin degradation promoting kinase GSK-3α/β was increased. Consistently, the protein levels of β-catenin downstream targets such as c-Myc and Cyclin Dl were also downregulated. Furthermore, the β-catenin-related EMT markers such as Slug and Snail were markedly suppressed by honokiol. Our findings indicate honokiol may be able to eliminate oral cancer stem cells through apoptosis induction, suppression of Wnt/β-catenin signaling, and inhibition of EMT. [ABSTRACT FROM AUTHOR]

Momordica charantia has been found to exhibit anticancer activity, in addition to its well-known therapeutic functions. We have demonstrated that the leaf extract of Momordica charantia ( MC ME) induces apoptosis in several human cancer cells through caspase- and mitochondria-dependent pathways. In this study, a different susceptibility to MC ME was found in human lung adenocarcinoma CL1 cells with different metastatic ability, leading to the significant difference of cell viability and invasiveness between MC ME-treated CL1-0 and CL1-5 cells. MC ME was found to upregulate the expression of Wnt-2 and affect the migratory and invasive ability of CL1 cells through suppressed M MP-2 and M MP-9 enzymatic activities.We proposed that MC ME mediates inhibition against migration of CL1 cells by reducing the expression and activation of Src and FAK to decrease the expression of downstream Akt, β-catenin, and M MPs. [ABSTRACT FROM AUTHOR]

HDAC inhibitors (HDACis) have been developed as promising anticancer agents in recent years. In this study, we synthesized and characterized a novel HDACi, termed NB M-HD-1. This agent was derived from the semisynthesis of propolin G, isolated from Taiwanese green propolis (TGP), and was shown to be a potent suppressor of tumor cell growth in human breast cancer cells ( MCF-7 and MDA-MB-231) and rat glioma cells (C6), with an IC50 ranging from 8.5 to 10.3 μ M.Western blot demonstrated that levels of p21(Waf1/Cip1), gelsolin, Ac-histone 4, and Ac-tubulin markedly increased after treatment of cancer cells with NB M-HD-1. After NB M-HD-1 treatment for 1-4 h, p-PTEN and p-AKT levels were markedly decreased. Furthermore, we also found the anticancer activities of NB M-HD-1 in regulating cell cycle regulators. Treatment with NB M-HD-1, p21(Waf1/Cip1) gene expression hadmarkedly increased while cyclin B1 and D1 gene expressions had markedly decreased. On the other hand, we found that NB MHD- 1 increased the expressions of tumor-suppressor gene p53 in a dose-dependent manner. Finally, we showed that NB M-HD-1 exhibited potent antitumor activity in a xenograft model. In conclusion, this study demonstrated that this compound, NB M-HD- 1, is a novel and potent HDACi with anticancer activity in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Tien-Hsien Liquid (THL) is a Chinese herbal mixture that has been used worldwide as complementary treatment for cancer patients in the past decade. Recently, THL has been shown to induce apoptosis in various types of solid tumor cells in vitro. However, the underlying molecular mechanisms have not yet been well elucidated. In this study, we explored the effects of THL on acute promyelocytic leukemia (APL) NB4 cells, which could be effectively treated by some traditional Chinese remedies containing arsenic trioxide. The results showed THL could induce G2/M arrest and apoptosis in NB4 cells. Accordingly, the decrease of cyclin A and B1 were observed in THL-treated cells. The THL-induced apoptosis was accompanied with caspase-3 activation and decrease of PML-RARa fusion protein. Moreover,DNA methyltransferase 1 and oncogenic signaling pathways such as Akt/mTOR, Stat3 and ERK were also down-regulated by THL. By using ethyl acetate extraction and silica gel chromatography, an active fraction of THL named as EAS5 was isolated. At about 0.5-1% of the dose of THL, EAS5 appeared to have most of THL-inducedmultiplemolecular targeting effects in NB4 cells. Based on the findings of these multi-targeting effects, THL might be regarding as a complementary and alternative therapeutic agent for refractory APL. [ABSTRACT FROM AUTHOR]

Aberrant activation of Wnt/β-catenin signaling plays an important role in the development of colon cancer. HS7 is an active fraction extracted from Taiwanofungus camphoratus, which had been widely used as complementary medicine for Taiwan cancer patients in the past decades. In this study, we demonstrated the effects of HS7 on the growth inhibition, apoptosis induction, and Wnt/β-catenin signaling suppression in human colon cancer cells. HS7 significantly inhibited proliferation ofHT29, HCT116, and SW480 colon cancer cells in a dose- and time-dependent manner. The apoptosis induction was evidenced by DNA fragmentation and subG1 accumulation, which was associated with increased Bax/Bcl-2 ratio, activation of caspase-3 and cleavage of PARP. By using Tcf-dependent luciferase activity assay, HS7 was found to inhibit the β-catenin/Tcf transcriptional activities. In addition, HS7 strongly suppressed the binding of Tcf complexes to its DNA-binding site shown in electrophoretic mobility shift assay. This inhibition was further confirmed by the decreased protein levels of Tcf-4 and β-catenin. The β-catenin/Tcf downstream target genes, such as survivin, c-myc, cyclin D1, MMP7, and MT1-MMP involved in apoptosis, invasion, and angiogenesis were also diminished as well. These results indicate that Taiwanofungus camphoratus may provide a benefit as integrative medicine for the treatment of colon cancer. [ABSTRACT FROM AUTHOR]