Effects of tyroservatide on histone acetylation in lung carcinoma cells.

Tyroservatide (YSV) is an active, low-molecular weight polypeptide shown to have antitumor effects on experimental hepatocarcinoma and lung carcinoma. The focus of our study was to observe the effects of YSV on several human lung carcinoma cell lines and explore its antitumor mechanism via its effect on histone acetylation. Our results showed that YSV significantly inhibited the proliferation of human lung carcinoma A549, NCIH460, NCIH292 and NCIH1299 cells, induced G(0) /G(1) cell cycle arrest and increased protein and mRNA levels of p21 and p27. Moreover, YSV treatment significantly inhibited histone deacetylase (HDAC) activity and resulted in the accumulation of acetylated histones H3 and H4 in total cellular chromatin and p21 gene-associated chromatin regions. Together these data suggest that the antitumor effects of YSV might be mediated by its inhibition of HDAC activity, selectively upregulating the expression of p21 by increasing the acetylation of histones associated with p21 gene regions, resulting in an induction of G0/G1 cell cycle arrest and inhibition of the proliferation of tumor cells. Our findings demonstrate that YSV may exhibit potent therapeutical effects on lung carcinoma.

The pentapeptide PLNPK inhibits systemic lupus erythematosus-associated renal damage.

OBJECTIVE: This study aimed to observe the therapeutic effect of pentapeptide PLNPK on systemic lupus erythematosus (SLE) in mice, and to study the inhibitory effect of PLNPK on activation of T cells in vivo. METHODS: Murine SLE-like chronic graft-versus-host disease (cGVHD) was induced. After treatment with PLNPK (100, 200, 400 µg/kg per day) for 70 days, serum blood urea nitrogen, creatine, total cholesterol, triglyceride and albumin were tested, and serum levels of anti-dsDNA and anti-histone antibodies were detected by ELISA. The pathological damage and IgG deposition in the kidney were identified. Concanavalin A (ConA)-induced T lymphocyte proliferation in SLE mice was also tested. RESULTS: PLNPK can reduce serum blood urea nitrogen, creatine, total cholesterol, triglyceride, and elevate serum albumin, and reduce levels of anti-dsDNA and anti-histone antibodies in the murine SLE model. Pathological damage and IgG deposition in the kidney were reduced in the PLNPK-treated group. PLNPK inhibited T lymphocyte infiltration in kidney tissues and ConA-induced T lymphocyte proliferation in SLE mice. CONCLUSION: Our results demonstrate that PLNPK can suppress T cell function and reduce the production of autoantibodies, and may be a feasible and effective therapy in the SLE model.

Effects of a novel tripeptide, tyroserleutide (YSL), on cell cycle progression of human hepatocellular carcinoma.

The objective of this study was to develop a new small molecular peptide, tyrosyl-seryl-leucine (tyroserleutide, YSL), as an anticancer drug. Our study investigated the effects of YSL on human hepatocellular carcinoma and cyclin, and explored its antitumor mechanism in vitro. In-vitro effects of YSL on human hepatocarcinoma cell BEL-7402 were assayed by the MTS (dimethylthiazol-carboxymethoxyphenyl-sulfophenyl - tetrazolium inner salt) method. The ultrastructure of tumor cells was observed by electron microscopy. DNA ladder was used to investigate apoptosis of BEL-7402 cells. The effects of YSL on the cell cycle of BEL-7402 cells were determined by flow cytometry. Expression of PCNA, P21, and P27 were investigated by real-time PCR and western blot in BEL-7402 cells. YSL inhibited the proliferation of BEL-7402 cells in vitro, induced DNA fragmentation, and changed their ultrastructure evidently, resulting in the necrosis and apoptosis of tumor cells. YSL interrupted cell cycle of tumor cells at G0/G1 and postponed their proceedings. YSL markedly enhanced the mRNA and protein expression of P21 and P27, and decreased the expression of PCNA of tumor cells. In conclusion, YSL significantly inhibited the growth of human hepatocellular carcinoma BEL-7402 cells and its anti-tumor effects may result from the upregulation of cyclin P21 and P27, and downregulation of cyclin PCNA.

The decapeptide CMS001 enhances swimming endurance in mice.

Now peptides achieve distinct advantages over protein in biological application because of its quick and easy absorption, low power, and high activity. Some bioactive peptides had been developed to be used in the management of exercise-related disorders. In this study, we investigated whether the decapeptide CMS001 (Pro-Thr-Thr-Lys-Thr-Tyr-Phe-Pro-His-Phe) isolated from pig spleen had anti-fatigue effects. Male Balb/c mice were administered CMS001 (20 microg/(kgd)(-1) or 5 microg/(kgd)(-1) for 30 d, intraperitoneal injections) and tested in an exhaustive swim time task. In order to examine the mechanisms of CMS001 anti-fatigue effects, we analyzed liver glycogen stores, blood urea nitrogen (BUN) levels, lactic acid levels, ultrastructural integrity, and levels of both a free radical metabolite and an anti-oxidant enzyme. CMS001 treatment prolonged exhaustive swim time, increased liver glycogen levels, reduced BUN levels, and decreased accumulation of lactic acid in the blood, relative to mice injected with only saline. Examination of the ultrastructure of mitochondria and sarcoplasmic reticulum in skeletal and cardiac muscle of CMS001-treated and control mice revealed that CMS001 can reduce the damage to cardiac and skeletal muscle caused by an exhaustive swim challenge, such that the structure of most tissue specimens were normal in the peptide-treated group. Furthermore the free radical analysis after acute exercise indicated that CMS001 treatment decreased malondialdehyde (MDA) and increased superoxide dismutase (SOD) levels. The present findings indicate that the spleen-derived peptide CMS001 has anti-fatigue effects in mice, and further suggest that the mechanism may involve reduction of tissue damaging free radicals in muscle tissues.

A new pentapeptide compound, PLNPK, ameliorates anti-glomerular basement membrane nephritis in Wistar rats.

PLNPK is a pentapeptide compound extracted from pig spleen with a Pro-Leu-Asn-Pro-Lys molecular structure. The spleen is the biggest immune organ in the body, in which there are lots of immunocytes and immune molecules. Our pilot study showed that PLNPK could suppress the transformation and proliferation of T lymphocytes and the production of antibodies in mice. It is widely accepted that most types of glomerulonephritis are immunological diseases caused by the reaction of antigen and antibody. Both humoral immunity and cell-mediated immunity contribute to the progress of these diseases, and suppression of immunoreactions and inflammation is important to ameliorate nephritis. After the immunosuppressive effects of this compound were discovered, this study also examined whether PLNPK had beneficial effects on a rat model of glomerulonephritis. The results suggested PLNPK (200microg/kg/d and 400microg/kg/d) reduced urinary protein excretion, lessened the deposit of autoantibodies along the glomerular basement membrane (GBM), reduced formation of crescent and protein casts, and ameliorated glomerular fibrosis and GBM injury. After treatment with PLNPK (200microg/kg/d and 400microg/kg/d) for 7 days, macrophage infiltration in the glomeruli was markedly reduced. Our results suggest that PLNPK has a beneficial effect on rat anti-GBM nephritis.

Inhibition of five xenografted human cancers and two murine cancers by the tripeptide tyroservatide.

The tripeptide tyroservatide (tyrosyl-seryl-valine, pTyr-Ser-Val-NH2) has been shown to have antitumor effects on experimental hepatocarcinoma. This study aimed to observe the effects of tyroservatide on other five human carcinomas: A549 (nonsmall cell lung carcinoma), BGC-823 (gastric cancer), MCF-7 (breast cancer), K562 (leukemia), A375 (melanoma) and two murine cancers: Lewis lung cancer and B16 (melanoma) in vivo. In vivo nude mice bearing xenografts of five different human tumors or C57BL/6 mice bearing xenografts of two different murine tumors were given daily intraperitoneal injections of tyroservatide or saline as controls, after tumor implantation. The inhibition of xenografts was determined by calculating the tumor volume and measuring tumor weight. Tyroservatide could significantly inhibit the growth of human lung carcinoma A549, human leukemia K562 and human melanoma A375 in nude mice (P<0.05). In addition, tyroservatide significantly inhibited the subcutaneous tumor growth of Lewis lung carcinoma and B16 melanoma (P<0.05). Tyroservatide, however, could not significantly suppress xenografts of BGC-823 and MCF-7 in nude mice (P>0.05). The results obtained indicate that tyroservatide exhibits different effects on different tumors, which will provide clinical applications guidance of tyroservatide as an anticancer drug.