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A new trithiodiketopiperazine derivative, adametizine C (1), and five new alkane derivatives (7–11), were isolated from the mangrove sediment–derived fungus Penicillium ludwigii SCSIO 41408, together with five known dithiodiketopiperazine derivatives (2–6). Their structures were elucidated on the basis of spectroscopic analysis, and the absolute configuration of 1 was determined by X-ray crystallographic analysis. In a variety of bioactivity screening, 1 – 5 exhibited some selective antifungal or antibacterial activities. Compounds 1 – 3 showed cytotoxicity against prostate cancer cell line 22Rv1 with half maximal inhibitory concentration (IC50) values of 13.0–13.9 μM; moreover, 3 showed obvious activity against another prostate cancer PC-3 cells with an IC50 value of 5.1 μM. Further experiments revealed that 3 could significantly reduce PC-3 cells colony formation and induce apoptosis in a dose-dependent manner. Several compounds also exhibited obvious inhibitory activities of lipopolysaccharide–induced nuclear factor-κB with IC50 values range from 8.2 to 21.5 μM, and 1 , 5 , and 9 were further evaluated for their effects on receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis. Adametizine C (1), with the strongest inhibitory activity against RANKL-induced osteoclast differentiation in bone marrow macrophage cells with 10 μM, was suggested to be the promising lead compound for the treatment of osteoclast-related diseases. [ABSTRACT FROM AUTHOR]

Matrine, an alkaloid compound isolated from Sophora flavescens Ait, has been shown to exert cancer‐killing actions in a variety of tumors; however, its anticancer mechanism in colorectal cancer (CRC) is not clear. The goal of our study was to characterize the anticancer effects and molecular mechanisms of matrine in SW480 CRC cells in vitro. Matrine treatment reduced mitochondrial metabolic function and ATP levels, repressed mitochondrial membrane potential, evoked mitochondrial reactive oxygen species accumulation, and promoted cyt‐c‐related mitochondrial apoptosis activation. In addition, we found that matrine treatment activated mitochondrial fission through upregulating mitochondrial elongation factor 1 (MIEF1); silencing of MIEF1 prevented matrine‐mediated mitochondrial damage and reversed the decrease in SW480 cell viability. Moreover, matrine treatment affected MIEF1 expression via the large tumor suppressor‐2 (LATS2)‐Hippo axis, and LATS2 deficiency suppressed the anticancer actions exerted by matrine on SW480 cancer cells. In summary, we show for the first time that matrine inhibits SW480 cell survival by activating MIEF1‐related mitochondrial division via the LATS2‐Hippo pathway. These findings explain the anticancer mechanisms of matrine in CRC and also identify the LATS2‐MIEF1 signaling pathway as an effective target for the treatment of CRC. [ABSTRACT FROM AUTHOR]

Accumulating evidence suggests that celecoxib and artemisinin could mediate ovarian cancer development and metastasis. The present study investigated the effects of celecoxib and artemisinin on the epithelial-mesenchymal transition (EMT) characteristics of the human ovarian epithelial adenocarcinoma cell line, SKOV3. SKOV3 cells were incubated with celecoxib (10 µM) for different periods of time to establish an EMT cell model. Subsequently, artemisinin (20, 40 and 80 µM) was used to establish a cell model of the reverse process, mesenchymal-epithelial transition (MET). Cell proliferation, metastasis, invasiveness and the expression of vimentin and E-cadherin were measured using Cell Counting Kit-8, wound healing assay, western blotting, flow cytometry and immunofluorescence. The EMT cell model exhibited enhanced proliferative capacity, increased migration, increased vimentin expression and decreased E-cadherin expression. By contrast, artemisinin decreased proliferative capacity, decreased migration, decreased vimentin expression and increased E-cadherin expression of EMT model cells, indicating that MET was induced. These results demonstrated that artemisinin may reverse celecoxib-induced epithelial-mesenchymal transition in SKOV3 cells. [ABSTRACT FROM AUTHOR]

Four new compounds, including two new polyketides, heterocornols M and N (1, 2), and a pair of epimers, heterocornols O and P (3, 4), were isolated from the fermentation broth of the marine sponge-derived fungus Pestalotiopsis heterocornis XWS03F09, together with three known compounds (5–7). The new chemical structures were established on the basis of a spectroscopic analysis, optical rotation, experimental and calculated electronic circular dichroism (ECD). All of the compounds (1–7) were evaluated for their cytotoxic activities, and heterocornols M-P (1–4) exhibited cytotoxicities against four human cancer cell lines with IC50 values of 20.4–94.2 μM. [ABSTRACT FROM AUTHOR]

Oxidative stress plays a dual role in tumor survival, either promoting tumor development or killing tumor cells under different conditions. Dankasterone A is a secondary metabolite derived from the fungus Talaromyces purpurogenu. It showed good potential in a screen for anti-prostate cancer compounds. In this study, MTT results showed dankasterone A was cytotoxic to prostate cancer cells, with an IC 50 of 5.10 μM for PC-3 cells and 3.41 μM for 22Rv1 cells. Further studies, plate cloning assays and real-time cell analysis monitoring showed that dankasterone A significantly inhibited clonal colony formation and cell migration in 22Rv1 and PC-3 cells. In addition, flow cytometry results showed that dankasterone A induced apoptosis in prostate cancer cells while having no impact on cell cycle distribution. At the molecular level, Protein microarray experiments and western blot assays revealed that dankasterone A specifically and dramatically upregulated HO-1 protein expression; and the results of cell fluorescence staining showed that dankasterone A induced overexpression of reactive oxygen species in 22Rv1 and PC-3 cells. Taken together, dankasterone A induced prostate cancer cells to undergo intense oxidative stress, which resulted in the production of large amounts of HO-1 and the release of large amounts of reactive oxygen species, leading to apoptosis of prostate cancer cells, ultimately resulting in the inhibition of both cell proliferation and migration. We also validated the anti-prostate cancer effects of dankasterone A in vivo in a zebrafish xenograft tumor model. In conclusion, dankasterone A has the potential to be developed as an anti-prostate cancer drug. [ABSTRACT FROM AUTHOR]

Prostate cancer is a disease that often occurs in elderly men. Androgen receptor signaling pathway runs through the occurrence and development of prostate cancer. Thereby, targeting androgen receptor is a crucial strategy for the treatment of prostate cancer. α-Terthienyl, which has been used as photosensitive activator and insecticide, is a natural compound rich in marigold. In the present study, we found α- terthienyl could inhibit the cell viability of four prostate cancer cell lines, especially on LNCaP and 22Rv1 cells which endogenously express androgen receptor. Then we proved that it could inhibit the proliferation of prostate cancer cells and induce apoptosis of prostate cancer cells by plate clone formation assay and flow cytometry respectively. Furthermore, we found α-terthienyl could inhibit androgen receptor nuclear translocation, reduce androgen receptor expression, reduce the mRNA and protein expression of androgen receptor target genes (KLK3, TMPRSS2, PCA3) and nuclear proliferation antigen Ki67 and PCNA. In addition, it inhibited the expression and phosphorylation of Akt protein while increasing the expression of tumor suppressor p27. Besides, we constructed a mouse xenograft prostate cancer model and confirmed that α-terthienyl also inhibited the growth of prostate cancer in vivo. In conclusively, α-terthienyl played an anti-prostate cancer role by inhibiting both the expression of androgen receptor and the transduction of its signal pathway, suggesting that it is a promising natural small molecule for the treatment of prostate cancer. [Display omitted] • α-Terthienyl inhibited the expression of androgen receptor and its target genes. • α-Terthienyl inhibited Akt expression and phosphorylation. • α-Terthienyl suppressed prostate cancer progression in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Six new casbane diterpenoids, sinularcasbanes G-L ( 1- 6, resp.) were isolated from the soft coral Sinularia sp. Their structures were established by extensive spectroscopic analyses, especially 2D-NMR and HR-ESI-MS. The configuration was confirmed by CD analyses and by comparison with data reported in the literature. The compounds were evaluated for cytotoxicity against ten human cancer cell lines (H1975, U937, K562, BGC823, MOLT-4, MCF-7, A549, HeLa, HL60, and Huh-7) and showed no activity. [ABSTRACT FROM AUTHOR]

Abstract: Four new cytochalasin derivatives (1–4), together with cytochalasin B (5), were isolated from the fungus Phoma sp. obtained from the giant jellyfish Nemopilema nomurai. The planar structure and relative stereochemistry were established by analysis of 1D and 2D NMR data. The absolute configuration was defined by the modified Mosher’s method. The compounds showed significant cytotoxicity against a small panel of human solid tumor cell lines (A549, SK-OV-3, SK-MEL-2, XF 498, and HCT15) with IC50 values in the range of 0.5–30μM. The cytochalasin B (5) showed obvious cytotoxicity with IC50 of 7.9μM against HeLa human cervical carcinoma cells. [Copyright &y& Elsevier]

Abstract: From the commercially available starfish Archaster typicus, five new (1–5) and 14 known (6–19) metabolites were isolated and identified. Detailed 1D and 2D NMR spectroscopic data, including 1H, 13C, DEPT, HSQC, HMBC, and NOESY, established the structures of the new metabolites as sodium 5α-cholesta-9(11),24-dien-3β,6α,20β-triol-23-one 3-sulphate (1), sodium 5α-cholesta-9(11)-en-3β,6α,20β-triol-23-one 3-sulphate (2), sodium (25R)-5α-cholestane-3β,4β,6α,8,14α,15β,26-heptaol-15-sulphate (3), sodium (25R)-5α-cholestane-3β,6α,8,14α,15β,26-hexaol 15-sulphate (4), and sodium cholest-25(27)-ene-3β,4β,5α,6α,7β,8β,14α,15α,24,26-decanol 6-sulphate (5). Other spectroscopic techniques, including IR, ESI–MS, and HR-ESI–MS, were also adopted to further confirm the structures of the metabolites. These five steroids (1–5) are reported in nature for the first time. All of the steroids found in A. typicus (1–12) were tested for anticancer activities against MDA-MB-435 and Colo205 tumour cells. However, only sodium 5α-cholesta-9(11)-en-3β,6α,20β-triol-23-one 3-sulphate (2) and 27-nor-5α-cholestane-3β,4β,5,6α,7β,8,14,15α,24α-nonaol (6) exhibited weak activities. [ABSTRACT FROM AUTHOR]

Abstract: Five new briarane type diterpenoids, dichotellides A−E (1−5), were isolated from the South China Sea gorgonian Dichotella gemmacea together with four known analogues (6−9). Compounds 1−5 represent the first examples of iodine-containing briarane type diterpenoids from nature. The structures of these diterpenoids were elucidated by spectroscopic analysis, including 1D, 2D-NMR, and HRESIMS, and the absolute configuration of 1 was further confirmed by single crystal X-ray diffraction analysis. All the isolates were evaluated for cytotoxicity activity against four human tumor cell lines, and only 3 exhibited marginal activity against SW1990 (human pancreatic cancer). [ABSTRACT FROM AUTHOR]

Abstract: Twenty-five new (abiesadines A–Y, 1–25) and 29 known (26–54) diterpenes were isolated from the aerial parts of Abies georgei. Abiesadine A (1) is a novel 8,14-seco-abietane, while abiesadine B (2) is a novel 9,10-seco-abietane. The structures of the new compounds were established on the basis of spectroscopic data analysis. Manool (52) showed the strongest effect against LPS-induced NO production in RAW264.7 macrophages with the IC50 value of 11.0μg/mL. In another anti-inflammatory assay against TNFα-triggered NF-κB activity, (12R,13R)-8,12-epoxy-14-labden-13-ol (54) exhibited the strongest effect (IC50 =8.7μg/mL). For antitumor assays, pomiferin A (26) and 8,11,13-abietatriene-7α,18-diol (29) both showed the most significant activity against LOVO cells (IC50 =9.2μg/mL). While 7-oxocallitrisic acid (46) exhibited significant cytotoxicity against QGY-7703 tumor cells (IC50 =10.2μg/mL). [Copyright &y& Elsevier]

We have reported the synthesis, structure-activity relationship study and anti-cancer activity evaluation of a series of Chrysamide B derivatives. [Display omitted] • The synthesis and structure-activity relationship study of Chrysamide B derivatives. • The most active compound b-9 inhibited multiple hallmarks of selected cancer cells. • Compound b-9 induced the mitochondrial-related apoptosis of selected cancer cells. • The JAK2/STAT3/Bcl-2 signaling pathway was possibly involved in the above apoptosis. Marine natural products derived from special or extreme environment provide an important source for the development of anti-tumor drugs due to their special skeletons and functional groups. In this study, based on our previous work on the total synthesis and structure revision of the novel marine natural product Chrysamide B, a group of its derivatives were designed, synthesized, and subsequently of which the anti-cancer activity, structure-activity relationships and cellular mechanism were explored for the first time. Compared with Chrysamide B, better anti-cancer performance of some derivatives against five human cancer cell lines (SGC-7901, MGC-803, HepG2, HCT-116, MCF-7) was observed, especially for compound b-9 on MGC-803 and SGC-7901 cells with the IC 50 values of 7.88 ± 0.81 and 10.08 ± 1.08 μM, respectively. Subsequently, cellular mechanism study suggested that compound b-9 treatment could inhibit the cellular proliferation, reduce the migration and invasion ability of cells, and induce mitochondrial-dependent apoptosis in gastric cancer MGC-803 and SGC-7901 cells. Furthermore, the mitochondrial-dependent apoptosis induced by compound b-9 is related with the JAK2/STAT3/Bcl-2 signaling pathway. To conclude, our results offer a new structure for the discovery of anti-tumor lead compounds from marine natural products. [ABSTRACT FROM AUTHOR]