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Peperomin E is a natural secolignan existing distributed in the plants of the genus Peperomia . Previous investigations demonstrated that peperomin E showed potential antitumor activity in some cancer lines, but it is unclear whether peperomin E has an effect on prostate cancer cell lines. The aim of the present study is to investigate its effects on proliferation inhibition, apoptosis-inducing and cell-cycle arrest activity using a prostate cancer PC-3 cell line. The proliferation inhibition was evaluated by MTT assay, apoptosis was detected by Annexin V/propidium iodide (PI) staining and Hoechst 33258 staining, cell cycle distributions were measured by flow cytometry, and western blot analysis was used to determine specific cellular apoptotic protein expressions of Bcl-2, Bax, caspase-3 and cleaved-caspase-3. According to the results of this study, peperomin E exhibited significant anti-proliferation activity on PC-3 cell lines in vitro in a dose-dependent manner. Peperomin E treatments lead to marked morphological changes. Apoptotic cell count and cell-cycle distribution at G2/M phase significantly increased with increasing concentrations of peperomin E. The down-regulated expression level of Bcl-2 and up-regulated expression level of Bax and cleaved-caspase-3 compared with the controls were also observed after peperomin E treatment. These data suggest that peperomin E exhibited proliferation inhabitation, apoptosis-inducing and cell-cycle arrest activity on PC-3 cell lines. The anti-proliferation effect of peperomin E on PC-3 cells should result partly from its cell-cycle arrest and apoptosis-inducing activity, whereas the increasing of the Bax/Bcl-2 ratio and activation of caspases-3 play an important role in the development of apoptosis.

Ovarian carcinoma is a tumor derived from ovary, which brings relatively higher mortality rate among the fatal gynecological cancers. Recently, lots of studies have concentrated on the anti-tumor effects of Arg-Gly-Asp (RGD) motif containing peptides due to their integrin binding properties. In order to meet the criterion of genetic engineering drugs, a recombinant RGD toxin protein (rLj-RGD3) without a His-tag was cloned from the buccal glands of Lampetra japonica in the present study. After endotoxin removal, the His-tag removed rLj-RGD3 was shown to inhibit the proliferation of HeyA8 cells. According to the confocal microscope, flow cytometry and western blot analysis, rLj-RGD3 could trigger HeyA8 cells apoptosis by changing mitochondrial membrane potential, arrangement of F-actin, protein level of BCL2, BAX, caspase 3, and cleaved caspase 3, concentration of cytoplasmic calcium, as well as phosphorylation level of ERK/JNK/p38. Furthermore, rLj-RGD3 was also able to suppress the adhesion, migration, and invasion processes of HeyA8 cells by disturbing the organization of F-actin and reducing the level of p-FAK. In addition, rLj-RGD3 could inhibit the adhesion of HeyA8 cells to extracellular matrix proteins by competitively binding to integrins, indicated that rLj-RGD3 might act as an anti-tumor drug to treat ovarian carcinoma patients in the future., (Copyright © 2016 Elsevier B.V. All rights reserved.)

As a critical evolutionary pivot between invertebrates and vertebrates, lampreys provide rich genetic information. Lamprey immune protein (LIP) is a key immune regulator. MicroRNAs, well-conserved in the response to immunological stress, remain understudied in lamprey immunity. We generated a lamprey microRNA expression atlas, using deep sequencing, upon Vibrio anguillarum infection. Using comparative methods, we found that miR-4561 potentially regulates innate immunity via interaction with lip. We found a sequence in the 3′-UTR region of LIP mRNA complementary to the miR-4561 seed region; miR-4561 expression was negatively correlated with LIP. During V. anguillarum infection, miR-4561 inhibited LIP expression and bacterial clearance. Notably, LIP expression in supraneural body cells was necessary for the Gram-negative immune response. Additionally, we observed that overexpression of miR-4561 induced apoptosis in embryonic cells, suggesting a role in embryonic development. Collectively, we show lamprey microRNAs may significantly affect gene regulation and provide new insights on LIP-mediated immune regulation. Ma et al characterise differentially expressed miRNAs in Lamprey upon bacterial infection. They identify miR-4561 as being decreased after infection and show that it targets the 3′UTR of the mRNA encoding lamprey immune protein (LIP) involved in lamprey innate immunity and regulates survival in lamprey embryos. [ABSTRACT FROM AUTHOR]

The non-receptor protein tyrosine kinase (nrPTK) Fyn, a member of the avian sarcoma virus transforming gene (Src) kinase family, plays a very significant role in cell growth, survival, apoptosis, tumor formation and immune response. In this study, a homolog of nrPTK Fyn was identified for the first time in the lamprey, Lampetra japonica and was named “Lja-Fyn”. The cDNA fragment of lamprey lja-fyn contains a 1611-bp open reading frame, which encodes a protein of 537 amino acids. Multiple sequence alignment analysis showed that it shares four conserved domains (Src homology (SH) 4, SH3, SH2 and protein kinases catalytic domains) and a variable unique domain with vertebrates Fyn molecules. Though Lja-Fyn has high sequence similarity with typical Fyn and Yes molecules of jawed vertebrates, the identities among Lja-Fyn and typical Fyn molecules in unique domain are relatively higher than that among Lja-Fyn and typical Yes molecules. The result indicates that Lja-Fyn is a homolog of Fyn rather than Yes. The phylogenetic analysis showed that Fyn, Yes and Src molecules are grouped into three distinct phylogenetic clusters, and Lja-Fyn is grouped as a single branch in Fyn cluster. The real-time quantitative PCR assay revealed the wide distribution of the lja-fyn mRNA in lamprey immune related tissues. After stimulation with mixed antigens, the levels of lja-fyn mRNA were obviously up-regulated in the gill and lymphocyte-like cells, and the similar results were got by western blot analysis of Lja-Fyn protein expression. These results indicated that nrPTK Lja-Fyn was likely to be involved in immune response. Furthermore, our present findings also provide the necessary information for understanding the distinction between lamprey Lja-Fyn and other members of jawed vertebrates in Src family. [ABSTRACT FROM AUTHOR]