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Two novel diterpenes Enhoidin A (1) and Enhoidin B (2) featuring an unusual gibberellane skeleton were isolated from the stems and leaves of Enhalus acoroides. Their structures were elucidated on the basis of spectroscopic analysis including 1D and 2D NMR techniques and HR-ESI-MS. This is the first time that this type of lactone ring between C-18 and C-20 has been found among gibberellanes from the tropical seagrasses. Evaluation of the all compounds for cytotoxicity against four human cancer cell lines (MCF-7, HCT-116, HepG-2 and HeLa), and showed moderate cytotoxic activities. [ABSTRACT FROM AUTHOR]

A new cadinane sesquiterpenoid glucoside, 2β,7,3-trihydroxycalamenene 3-O-β-d-glucoside (1) together with six known compounds, N-(p-trans-coumaroyl)-N-methyl tyramine (2), Cleomiscosin A (3), 9,12,13-trihydroxy-10,15-heptadecadienoic acid (4), Cytochalasin B (5), Marmesinin (6) and N-(p-trans-coumaroyl) tyramine (7) were obtained from the stem bark of Abelmoschus sagittifolius. The new structure of compound 1 was elucidated by analysing its 1H and 13C-NMR, 1H-1H COSY, HSQC, HMBC, NOESY and HR-ESI-MS spectra. Compounds 1–7 showed moderate cytotoxicity against Hela and HepG-2 human cancer cell lines. [ABSTRACT FROM AUTHOR]

Background/Aims: This study focused on the oncogenic role of Diphthamide biosynthesis 1 (DPH1) in colorectal cancer (CRC) cells. Methods: The expression of DPH1 was determined by quantitative RT-PCR analysis and western blotting in CRC tissues. The role of DPH1 in CRC cells was investigated via cell viability and invasion assays under the condition of DPH1 silencing or overexpression. Bioinformatics analysis and luciferase reporter analysis were used to identify the upstream microRNA which might regulate DPH1.The inverse correlation between the microRNA and DPH1 was also detected in CRC cells. Results: We identified an unexpected role for DPH1 as an oncogene in CRC cells. The tumour-suppressive miR-218-5p regulates DPH1 directly and negatively. Loss of miR-218-5p drives the oncogenic role of DPH1 in CRC cells. Conclusion: The modulation of DPH1 by miR-218-5p may be an important regulatory axis during CRCtumourigenesis. [ABSTRACT FROM AUTHOR]

[Display omitted] • Three new cadinene-type sesquiterpene dimers, named hibisceusones A-C, were isolated from H. tiliaceus. • Dimeric skeletons were formed from a unique 1,4-dioxane ring for the first time in natural products. • Compound 2 exhibited promising anti-TNBC activities by inducing the apoptosis of MDA-MB-231 cells by inhibiting the PI3Kα pathway. Three new cadinane-type sesquiterpenoid dimeric diastereomers (1 – 3) named hibisceusones A-C were obtained from the infected stems of Hibiscus tiliaceus. The structures were determined by NMR spectroscopy and MS techniques, and the absolute configurations were assigned by ECD and single-crystal X-ray diffraction techniques. Compounds 1 – 3 are diastereomers, and contain a 1,4-dioxane ring linearly fused to different cadinane-type polycyclic skeletons. This is the first time that such a structure has been identified in natural products. Compounds 1 – 3 exhibited cytotoxic activities, and 2 showed a significantly high anti-triple-negative breast cancer (TNBC) effect. The anti-cancer effect of compound 2 was 3–4 fold higher than that of 1 and 3. The anti-cancer effect was generated via the induction of the apoptosis of the MDA-MB-231 cells by inhibiting the PI3Kα pathway. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs), a class of small noncoding RNAs that regulate target gene expression, play an important role in cancer initiation, progression, and metastasis. However, the role of many miRNAs in cervical cancer is not fully understood. In this study, we found that miR-212 and miR-132 from the same gene cluster are downregulated in human cervical cancer tissues when compared with adjacent noncancerous tissues. The overexpression of miR-212/132 not only led to a delay in the G1/S phase transition and repressed cell proliferation but also resulted in an increase in E-cadherin expression and a decrease in vimentin, suppressing the epithelial to mesenchymal transition and migration and invasion in cervical cancer cells. Subsequently, SMAD2 was identified as a common target of miR-212/132 and was found to be negatively regulated by miR-212/132 at the mRNA and protein levels. Furthermore, SMAD2 silencing led to the same effect on cervical cancer cells as miR-212/132 overexpression. Importantly, SMAD2 overexpression partially reversed the cellular phenotypes induced by miR-212/132 overexpression. In conclusion, our study indicated that miR-212/132 functions as tumor suppressor by targeting SMAD2 in cervical cancer. © 2015 IUBMB Life, 2015 67(5):380-394, 2015 [ABSTRACT FROM AUTHOR]

Nischarin is an integrin-binding protein, which is well known as a novel tumor suppressor. In breast cancer, Nischarin serves a critical role in breast cancer cell migration and invasion. However, the molecular mechanism underlying the role of Nischarin remains unclear. Recent findings have demonstrated that epithelial-mesenchymal transition (EMT) increases the capacity of cell migration and invasion. As a member of the integrin family, it was hypothesized that Nischarin may regulate cellular processes via various signaling pathways associated with the EMT process. The present study detected the mRNA levels of EMT regulators via reverse transcription-quantitative PCR and related protein levels via western blotting in breast cancer cells, following NISCH-overexpression and -knockdown. The results demonstrated that Nischarin inhibits cell proliferation, migration and invasion in breast cancer cells. Furthermore, when the NISCH gene was overexpressed, the relative mRNA level of E-cadherin was increased, while the relative mRNA levels of several transcription factors, such as Snail, ZEB1, N-cadherin, Slug, Twist1 and vimentin, decreased. When NISCH was silenced, these results were reversed. The present results demonstrated that Nischarin suppresses cell migration and invasion via inhibiting the EMT process. [ABSTRACT FROM AUTHOR]

Five new cucurbitane-typetriterpenoid glycosides, named Xuedanoside F–J (1–5), were obtained from the rhizomes of Hemsleya penxianensis (Xue dan), which belongs to the family of Cucurbitaceae. These new compounds were elucidated byspectroscopic analysis, including 1D, 2D NMR, and HR-ESI-MS spectra. Additionally, all the isolates were evaluated for cytotoxicity against three human cancer cell lines (Hela, MCF-7, and A-549) with the IC50 ranging from 2.25 to 49.44 µM in vitro with treatment 48 h and showed low cytotoxicity in human normal liver L-02 cells (IC50 > 50 µM). Compound 5 showed the most significant cytotoxic activity with the IC50 value of 2.25, 4.72, and 5.33 µM in 48 h, respectively. [ABSTRACT FROM AUTHOR]

Natural daphnane diterpenoids, mainly distributed in plants of the Thymelaeaceae and Euphorbiaceae families, usually include a 5/7/6-tricyclic ring system with poly-hydroxyl groups located at C-3, C-4, C-5, C-9, C-13, C-14, or C-20, while some special types have a characteristic orthoester motif triaxially connectedat C-9, C-13, and C-14. The daphnane-type diterpenoids can be classified into five types: 6-epoxy daphnane diterpenoids, resiniferonoids, genkwanines, 1-alkyldaphnanes and rediocides, based on the oxygen-containing functions at rings B and C, as well as the substitution pattern of ring A. Up to now, nearly 200 daphnane-type diterpenoids have been isolated and elucidated from the Thymelaeaceae and Euphorbiaceae families. In-vitro and in-vivo experiments of these compounds have shown that they possess a wide range of biological activities, including anti-HIV, anti-cancer, anti-leukemic, neurotrophic, pesticidal and cytotoxic effects. A comprehensive account of the structural diversity is given in this review, along with the cytotoxic activities of daphnane-type diterpenoids, up to April 2019. [ABSTRACT FROM AUTHOR]

PDB-1 inhibits cell proliferation by downregulating the expression of CDK1 and cyclin B1 and upregulating the expression of p21 to induce cell G2/M phase arrest. PDB-1 induces autophagy and apoptosis of tumor cells, by down-regulation the PI3K/AKT/mTOR pathway. These data provide a new clue to understand the potential antitumor mechanism of PDB-1 in A549 cells. • PDB-1 has significant selectivity to cancer cell lines, particularly for A549. • PDB-1 inhibits A549 proliferation and colony formation by arresting G2/M cell cycle. • PDB-1 can induce apoptosis and autophagy by inactivating the mTOR/PI3K/AKT pathway. PDB-1 is a new C-27-carboxylated-lupane-triterpenoid derivative isolated from Potentilla discolor Bunge. In our previous research, PDB-1 was suggested to have an obvious selectivity for tumor cells. This study focused on clarifying PDB-1's anticancer mechanism in the inhibition of proliferation and in the induction of apoptosis and autophagy in A549 cells. In general, A549 cells were treated with PDB-1 for different times, and cell survival was assessed by a CCK8 assay. The assessment of intracellular reactive oxygen species, a mitochondrial membrane potential assay, a cell cycle assay, an annexin V-FITC/PI assay, and MDC staining were performed in A549 cells treated with PDB-1. Moreover, the mRNA and protein expression of cell cycle-, apoptosis- and autophagy-related factors were detected by RT-qPCR and western blotting. The results showed that PDB-1 inhibited A549 cell proliferation and colony formation in a dose- and time-dependent manner. The decrease in the viability of A549 cells was due to a G2/M cell cycle arrest. Moreover, PDB-1 induced cell apoptosis, accompanied by an increase in the Bax/Bcl-2 ratio and an increase in the expression levels of cleaved caspase-3/caspase-9. We also found that PDB-1 induced autophagy by increasing the conversion of LC3-I to LC3-II and elevating Beclin-1. In addition, further studies indicated that pretreatment with a specific PI3K inhibitor (LY294002) enhanced the effects of PDB-1 on the expression of proteins associated with apoptosis and autophagy, demonstrating that the PI3K/Akt/mTOR pathway was related to PDB-1-induced apoptosis and autophagy. These results indicated that PDB-1 may be considered a potential candidate for the future treatment of lung adenocarcinoma. These findings should benefit the development of the C 14 -COOH type of pentacyclic triterpenoids. [ABSTRACT FROM AUTHOR]