Prodigiosin, a secondary metabolite red pigment produced by Serratia marcescens, has an interesting apoptotic efficacy against cancer cell lines with low or no toxicity on normal cells. HSP90α is known as a crucial and multimodal target in the treatment of TNBC. Our research attempts to assess the therapeutic potential of prodigiosin/PU-H71 combination on MDA-MB-231 cell line. The transcription and protein expression levels of different signalling pathways were assessed. Treatment of TNBC cells with both drugs resulted in a decrease of the number of adherent cells with apoptotic effects. Prodigiosin/PU-H71 combination increased the levels of caspases 3,8 and 9 and decreased the levels of mTOR expression. Additionally, there was a remarkable decrease of HSP90α transcription and expression levels upon treatment with combined therapy. Also, EGFR and VEGF expression levels decreased. This is the first study to show that prodigiosin/PU-H71 combination had potent cytotoxicity on MDA-MB-231 cells; proving to play a paramount role in interfering with key signalling pathways in TNBC. Interestingly, prodigiosin might be a potential anticancer agent to increase the sensitivity of TNBC cells to apoptosis. This study provides a new basis for upcoming studies to overcome drug resistance in TNBC cells.

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Background: In the context of searching for potent, safe, natural antimicrobial agents to combate the global antimicrobial resistance (AMR) phenomenon, the current study evaluates for the first time ever, the broad-spectrum antimicrobial activity of essential oil (EO) and extracts from the rare wild plant Centaurea pumilio L.. It has tremendous ethnomedicinal values; its dried root is used as a fattening agent, a treatment for bad breath and diabetes, and screened for schistosomicidal activity. Methods: C. pumilio EO was extracted by hydrodistillation using a Clevenger apparatus. Chemical constituents of aerial part were extracted using a sequential solvent/solvent procedure employing four solvents with increasing polarities in the following order: petroleum ether, chloroform, ethyl acetate, and n-butanol. The chemical constituents were identified by GC-MS. Fifty-two microbial strains were used; twenty-six multidrug resistant (MDR), sixteen clinical, and ten reference strains. The identification of the microbial strains was performed by MALDI-TOF-MS. The antimicrobial activity of the EO and the aerial part and the root extracts was assessed through disc diffusion assay. A minimum inhibitory concentration (MIC) of the EO and extracts was determined using the broth micro-dilution method. Results: The growth of reference and clinical strains was inhibited by EO, methanol, chloroform, and ethyl acetate aerial part extracts and chloroform root extract. The MDR strains growth, however, was inhibited only by EO and chloroform aerial part extract. GC-MS identified for the first time eighteen constituents from aerial part EO and chloroform extract each. EO showed antimicrobial activity against the reference, clinical, and MDR strains with MIC values of 31.25-125, 31.25-125, and 62.50-250 μg/mL, respectively. Methanol aerial part extract exhibited high antimicrobial activities with MIC values of 62.50-250 μg/mL against reference and clinical strains. Chloroform root extract displayed strong antimicrobial activity against reference and clinical strains recording MIC values of 62.50-250 μg/mL and 62.50-125 μg/mL, respectively. The chloroform aerial part extract demonstrated potent antimicrobial activity against the reference, clinical, and MDR strains with 31.25, 31.25, and 15.62 μg/mL MIC values, respectively.

Bacteriocins, ribosomally synthesized antimicrobial peptides, display potential applications in agriculture, medicine, and industry. The present study highlights integral statistical optimization and partial characterization of a bacteriocin substance from a soil bacterium taxonomically affiliated as Bacillus sp. YAS 1 after biochemical and molecular identifications. A sequential statistical approach (Plackett-Burman and Box-Behnken) was employed to optimize bacteriocin (BAC YAS 1) production. Using optimal levels of three key determinants (yeast extract (0.48% (w/v), incubation time (62 hrs), and agitation speed (207 rpm)) in peptone yeast beef based production medium resulted in 1.6-fold enhancement in BAC YAS 1 level (470 AU/mL arbitrary units against Erwinia amylovora). BAC YAS 1 showed activity over a wide range of pH (1–13) and temperature (45–80°C). A wide spectrum antimicrobial activity of BAC YAS 1 against the human pathogens (Clostridium perfringens, Staphylococcus epidermidis, Campylobacter jejuni, Enterobacter aerogenes, Enterococcus sp., Proteus sp., Klebsiella sp., and Salmonella typhimurium), the plant pathogen (E. amylovora), and the food spoiler (Listeria innocua) was demonstrated. On top and above, BAC YAS 1 showed no antimicrobial activity towards lactic acid bacteria (Lactobacillus bulgaricus, L. casei, L. lactis, and L. reuteri). Promising characteristics of BAC YAS 1 prompt its commercialization for efficient utilization in several industries.