Proline-rich Polypeptide-1 Protects the Cells In Vitro from Genotoxic Effects of Mitomycin C

Aroutiounian, Rouben; Hovhannisyan, Galina; Gasparyan, G. H.; Margaryan, K.; Aroutiounian, D. N.; Sarkissyan, N. K.; Galoyan, A. A.

doi:10.1007/s11064-009-0104-8

Cited by 5 publications

(4 citation statements)

References 16 publications

(18 reference statements)

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“…Several free radical scavenger agents, such as amifostine, proline-rich polypeptide and nitroxide, prevented the cytotoxic damage mediated by MMC in different organisms (Krishna et al 1991;Hahn et al 1997;Santini 2001;Aroutiounian et al 2010). Likewise, it was suggested that apigenin and quercetin (bioflavonoids) exhibited protection against the MMC genotoxicity on mice bone marrow cells (Siddique and Afzal 2009;Mazumdar et al 2011).…”

Section: Discussionmentioning

confidence: 99%

Xanthoria elegans (Link) (lichen) extract counteracts DNA damage and oxidative stress of mitomycin C in human lymphocytes

2012

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Several lichen species have been used for medicinal purposes throughout the ages, and they are reported to be effective in the treatment of different disorders including ulcer and cancer. It is revealed that lichens may be easily accessible sources of natural drugs and possible food supplements after their safety evaluations. The main objective in this study was to evaluate the roles of aqueous extracts of Xanthoria elegans (at 25, 50 and 100 lg/ml) upon mitomycin C (MMC; at 10 -7 M) induced genotoxic and oxidative damages in cultured human lymphocytes. X. elegans were collected from the Erzurum and Artvin provinces (in Turkey) during August 2010. After the application of MMC and X. elegans extract (XEE), separate and together, human whole blood cultures were assessed by four genotoxicity end-points including chromosomal aberration, micronucleus, sister chromatid exchange (SCE) and 8-oxo-2-deoxyguanosine (8-OHdG) assays. In addition, biochemical parameters [total antioxidant capacity (TAC) and total oxidative stress (TOS)] were examined to determine oxidative effects. According to our results, the frequencies of cytogenetic endpoints and 8-OH-dG levels were significantly increased by MMC compared with controls in human peripheral lymphocytes. MMC caused oxidative stress by altering TAC and TOS levels. On the contrary, XEE led to increases of TAC level without changing TOS level. XEE had no genotoxic effect. Furthermore, our findings revealed that MMC induced increases in the mean frequencies of four genotoxic indices were diminished by XEE in dose dependent manner, indicating its protective role towards cells from MMC exerted injury. In conclusion, the results obtained in the present study indicate for the first time that XEE is a potential source of natural antigenotoxicants.

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Section: Discussionmentioning

confidence: 99%

Xanthoria elegans (Link) (lichen) extract counteracts DNA damage and oxidative stress of mitomycin C in human lymphocytes

2012

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“…PRP-1 is a mediator of the hypothalamus neurohypophysis-bone marrow axis as well as a powerful immunomodulator [1,2] and has many metabolic properties, including antitumorigenic [3][4][5][6][7][8]24]. The observed antineoplastic effect was not mediated by genotoxicity or chromosomal instability [9,10]. PRP-1 stimulated normal human marrow stromal cells but had an inhibitory effect on human giant cell tumor stromal cells [11].…”

Section: Introductionmentioning

confidence: 99%

Cytostatic effect of novel mTOR inhibitor, PRP-1 (galarmin) in MDA 231 (ER−) breast carcinoma cell line. PRP-1 inhibits mesenchymal tumors

2011

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Activation of the PI3K-Akt-mTOR pathway is implicated both in the establishment of tumors and as well as a target for therapy in many types of solid malignancy, its blockade represents an opportunity to improve outcomes in patients with tumors that are associated with poor prognosis. Our experimental data indicates that proline-rich polypeptide-1 (PRP-1, galarmin) is immunomodulator cytokine, produced by hypothalamic neurosecretory cells and exerts its antiproliferative effect on the tumor cells of mesenchymal origin via inhibiting mTOR kinase activity and repressing cell cycle progression. The goal of these investigations was to elucidate the antiproliferative action of PRP-1 on the breast carcinoma cell line MDA 231 (ER-) and to compare PRP-1 action previously reported on other mesenchymal tumors. These experiments confirmed maximum inhibition of cell growth at 0.5 and 1 μg/ml PRP-1 (71% and 63%, respectively) and inhibition at 10 μg/ml of 44%. There was no inhibitory effect observed on luminal T47-D (ER+) cells. Videomicroscopy results demonstrated dividing cells in the cytokine-treated MDA 231 (ER-), suggesting that the cells were not in the state of dormancy. The flow cytometry experiments confirmed that PRP-1-treated cells were accumulated in S phase. No apoptosis, caspase activation, or senescence was detected after treatment with this cytokine. Experiments with mTOR with PRP-1 (10 μg/ml) indicated statistically significant 40% inhibition of mTOR kinase activity in immunoprecipitates of the MDA 231 (ER-) cell line. PRP-1 is a novel mTOR inhibitor with strong antiproliferative action in mesenchymal tumors mostly resistant to radiation and chemotherapy.

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“…AgTriAll4PyMVanC 16 P added to KCL-22 cells at concentrations IC 50 /5 and IC 50 was shown to induce the breakage of DNA molecule 2 h after application (Table 3). However, the observed level of DNA damage is known to be reparable [58] and not to lead to heritable DNA/chromosome damage or to the cell death [59]. Thus, amphiphilic Ag porphyrin could induce early dose-dependent slow, transient and reparable DNA lesions.…”

Section: Resultsmentioning

confidence: 99%

Novel amphiphilic cationic porphyrin and its Ag(II) complex as potential anticancer agents

Tovmasyan

Babayan

Poghosyan

et al. 2014

Journal of Inorganic Biochemistry

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In the present study we have synthesized a novel amphiphilic porphyrin and its Ag(II) complex through modification of water-soluble porphyrinic structure in order to increase its lipophilicity and in turn pharmacological potency. New cationic non-symmetrical meso-substituted porphyrins were characterized by UV–visible, electrospray ionization mass spectrometry (ESI-MS), 1H NMR techniques, lipophilicity (thin-layer chromatographic retention factor, Rf), and elemental analysis. The key toxicological profile (i.e. cytotoxicity and cell line-(cancer type-) specificity; genotoxicity; cell cycle effects) of amphiphilic Ag porphyrin was studied in human normal and cancer cell lines of various tissue origins and compared with its water-soluble analog. Structural modification of the molecule from water-soluble to amphiphilic resulted in a certain increase in the cytotoxicity and a decrease in cell line-specificity. Importantly, Ag(II) porphyrin showed less toxicity to normal cells and greater toxicity to their cancerous counterparts as compared to cisplatin. The amphiphilic complex was also not genotoxic and demonstrated a slight cytostatic effect via the cell cycle delay due to the prolongation of S-phase. As expected, the performed structural modification affected also the photocytotoxic activity of metal-free amphiphilic porphyrin. The ligand tested on cancer cell line revealed a dramatic (more than 70-fold) amplification of its phototoxic activity as compared to its water-soluble tetracationic metal-free analog. The compound combines low dark cytotoxicity with 5 fold stronger phototoxicity relative to Chlorin e6 and could be considered as a potential photosensitizer for further development in photodynamic therapy.

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Proline-rich Polypeptide-1 Protects the Cells In Vitro from Genotoxic Effects of Mitomycin C

Cited by 5 publications

References 16 publications

Xanthoria elegans (Link) (lichen) extract counteracts DNA damage and oxidative stress of mitomycin C in human lymphocytes

Xanthoria elegans (Link) (lichen) extract counteracts DNA damage and oxidative stress of mitomycin C in human lymphocytes

Cytostatic effect of novel mTOR inhibitor, PRP-1 (galarmin) in MDA 231 (ER−) breast carcinoma cell line. PRP-1 inhibits mesenchymal tumors

Novel amphiphilic cationic porphyrin and its Ag(II) complex as potential anticancer agents

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