Doxorubicin metabolism moderately attributes to putative toxicity in prodigiosin/doxorubicin synergism in vitro cells.

Doxorubicin (Dox) is a widely neoplasm chemotherapeutic drug with high incidences of cardiotoxicity. Prodigiosin (PG), a red bacterial pigment from Serratia marcescens, has been demonstrated to potentiate Dox's cytotoxicity against oral squamous cell carcinoma cells through elevating Dox influx and identified as a Dox enhancer via PG-induced autophagy; however, toxicity of normal cell remains unclear. This study is conducted to evaluate putative cytotoxicity features of PG/Dox synergism in the liver, kidney, and heart cells and further elucidate whether PG augmented Dox's effect via modulating Dox metabolism in normal cells. Murine hepatocytes FL83B, cardio-myoblast h9c2, and human kidney epithelial cells HK-2 were sequentially treated with PG and Dox by measuring cell viability, cell death characteristics, oxidative stress, Dox flux, and Dox metabolism. PG could slightly significant increase Dox cytotoxicity in all tested normal cells whose toxic alteration was less than that of oral squamous carcinoma cells. The augmentation of Dox cytotoxicity might be attributed to the increase of Dox-mediated ROS accumulation that might cause slight reduction of Dox influx and reduction of Dox metabolism. It was noteworthy to notice that sustained cytotoxicity appeared in normal cells after PG and Dox were removed. Taken together, moderately metabolic reduction of Dox might be ascribed to the mechanism of increase Dox cytotoxicity in PG-induced normal cells; nevertheless, the determination of PG/Dox dose with sustained cytotoxicity in normal cells needs to be comprehensively considered.

Identification of anisomycin, prodigiosin and obatoclax as compounds with broad-spectrum anti-parasitic activity.

Parasitic infections are a major source of human suffering, mortality, and economic loss, but drug development for these diseases has been stymied by the significant expense involved in bringing a drug though clinical trials and to market. Identification of single compounds active against multiple parasitic pathogens could improve the economic incentives for drug development as well as simplifying treatment regimens. We recently performed a screen of repurposed compounds against the protozoan parasite Entamoeba histolytica, causative agent of amebic dysentery, and identified four compounds (anisomycin, prodigiosin, obatoclax and nithiamide) with low micromolar potency and drug-like properties. Here, we extend our investigation of these drugs. We assayed the speed of killing of E. histolytica trophozoites and found that all four have more rapid action than the current drug of choice, metronidazole. We further established a multi-institute collaboration to determine whether these compounds may have efficacy against other parasites and opportunistic pathogens. We found that anisomycin, prodigiosin and obatoclax all have broad-spectrum antiparasitic activity in vitro, including activity against schistosomes, T. brucei, and apicomplexan parasites. In several cases, the drugs were found to have significant improvements over existing drugs. For instance, both obatoclax and prodigiosin were more efficacious at inhibiting the juvenile form of Schistosoma than the current standard of care, praziquantel. Additionally, low micromolar potencies were observed against pathogenic free-living amebae (Naegleria fowleri, Balamuthia mandrillaris and Acanthamoeba castellanii), which cause CNS infection and for which there are currently no reliable treatments. These results, combined with the previous human use of three of these drugs (obatoclax, anisomycin and nithiamide), support the idea that these compounds could serve as the basis for the development of broad-spectrum anti-parasitic drugs.

Effect of prodigiosin on the alleviation of the intestinal inflammation of weaned rats based on 1H-NMR spectroscopy study and biochemistry indexes

Weaning results in intestinal dysfunction, mucosal atrophy, transient anorexia, and intestinal barrier defects. In this study, the effect of prodigiosin (PG) on the intestinal inflammation of weaned rats was investigated by using 1H-NMR spectroscopy and biochemistry indexes to regulate the intestinal metabolism. After administration for 14 days, the body mass of the PG group was increased by 1.29- and 1.26-fold compared with those of the control and alcohol groups, respectively, using a dose of 200 µg PG·kg-1 body weight per day. PG increased organic acid content and decreased moisture, pH values, and free ammonia in feces. In addition, PG alleviated the intestinal inflammation of weaned rats. The analysis of 1H-NMR signal peak attribution and the model validation of metabolic data of feces contents showed that PG significantly affected the metabolism of small molecular compounds in the intestinal tract of weaned rats. This study presents the promising alternative of using PG to alleviate intestinal inflammation effectively in the intestinal tract of weaned rats.

Differential genomic damage in different tumor lines induced by prodigiosin.

Prodigiosin is a secondary metabolite produced by Serratia marcercens. As this pigment is suggested to be a cancer drug, genotoxicity studies are necessary. The aim of the present investigation was to evaluate the genotoxic effects of prodigiosin on tumoral and normal cell lines, NCIH-292, MCF-7 and HL-60. A normal line BGMK was used as control. Genomic damage induced by prodigiosin was observed in all tumor lines as well as the control line. The pigment induced the formation of micronuclei in tumor cells. The present data confirm the antitumor potential of prodigiosin. However, these findings also raise concerns regarding its target-specific action, as genotoxic effects on normal cells also occurred.

[Effectiveness of treating chronic cholecystitis by prodigiozain electrophoresis]. / Ob éffektivnosti lechenii élektroforezom prodigiozana bol'nykh khronicheskim kholetsistitom

136 patients suffering from chronic cholecystitis were treated in the phase of exacerbation with antibiotics in combination with prodigiosan. It was found that inclusion of prodigiosan into the therapeutic complex had a positive effect on the immediate and late results of the treatment. Since intramuscular administration of prodigiosan was accompanied by a number of side effects, a method of the drug administration by means of electrophoresis on the area of the bile bladder was tested. It was shown that prodigiosan administered by the method of electrophoresis totally preserved its stimulating capacity with respect to the host. As with intramuscular administration of prodigiosan, the general reaction of the host and positive dynamics of the clinical and laboratory indices of the active process were observed and the content of lysozyme in the blood phagocytes reliably increased. The method of prodigiosan administration by means of electrophoresis was better tolerated by the patients and no side effects characteristic of the drug intramuscular administration were noted. When indicated, the use of prodigiosan by means of electrophoresis is recommended.