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Focal-adhesion evaluation after PG or OBX treatment in SK-MEL-5 (A–C) and in SK-MEL-28 (D–F). Immunofluorescence of vinculin (red) and actin (green) shows focal adhesions in SK-MEL-5 (A) and SK-MEL-28 (D) cells after 3 h of treatment with PG (1 or 4 µM, respectively) or OBX (10 µM). The percentage of focal adhesions (B,E), as well as the percentage of cell attachment (C,F), were quantified. Figure shows mean ± SD. Statistical differences from control (CTRL) are shown as ** p < 0.01 and * p < 0.05.
Source publication
Metastasis is the primary cause of death in cancer patients. Many current chemotherapeutic agents only show cytotoxic, but not antimetastatic properties. This leads to a reduction in tumor size, but allows cancer cells to disseminate, which ultimately causes patient death. Therefore, novel anticancer compounds with both effects need to be developed...
Citations
... However, current findings have shown the potential of using OBT in eradicating therapy resistance in cancer cells as well as leukemia, specifically cancer stem cells. However, the matter of toxicity of OBT has been raised with reference to clinical trials and needs to be considered as well (Espona-Fiedler et al., 2022;Gao et al., 2023;Kaushik et al., 2018;Liang et al., 2015). ...
Ionophores, a class of animal antibiotics, are widely used in intensive livestock
farming to enhance feed efficiency and control coccidiosis. These compounds,
known for their ability to transport cations across biological membranes, are
crucial in maintaining cellular homeostasis. However, their extensive use
raises environmental and human health concerns. This manuscript offers a
comprehensive review of ionophores in livestock production, highlighting
their environmental impact and potential to contribute to antimicrobial resistance
(AMR). It emphasizes the fate and transport of ionophores in various
environmental matrices, providing a holistic framework for assessing ecological
risks. The study calls for improved management practices like enhanced
waste management through anaerobic digestion, and composting is essential.
Establishing Maximum Residue Limits (MRLs) and using LC–MS/MS for residue
detection will help manage exposure. Educating livestock producers and
researching alternatives like probiotics can decrease reliance on ionophores to
mitigate the ecological footprint of ionophores, making it a timely and relevant
piece of research. Ionophores can persist in the environment, potentially contributing
to AMR in gram-positive bacteria. Furthermore, their presence in
manure, runoff, and agricultural soils has been documented, leading to contamination
of water bodies and sediments. Ionophores pose risks to terrestrial
and aquatic ecosystems, with studies revealing hazardous effects even at low
concentrations. This review highlights the need for improved management
practices to mitigate the environmental impacts of ionophores, particularly
regarding AMR development and ecosystem disruption. Careful monitoring
and sustainable use of these antibiotics are essential to reduce their ecological
footprint in livestock production.
... We assessed the drug sensitivity of melanoma patients by analyzing the IC50 values of various drugs, as determined by the pRRophetic package, across high-risk and lowrisk groups. Among the drugs tested, several chemotherapeutic agents, such as Nilotinib, Sorafenib, GX15-070, and Cisplatin, have been reported in the literature for their potential therapeutic use in melanoma treatment (31)(32)(33)(34). Finally, the results were depicted in a bar diagram ( Figure 5E). ...
Background
Cutaneous melanoma is a type of malignant tumor that is challenging to predict and is readily stimulated by various factors. Oxidative stress can induce damage and alterations in melanocytes, subsequently triggering immune responses. Given that oxidative stress is a prevalent tumor stimulus, we aimed to enhance melanoma prediction by identifying lncRNA signatures associated with oxidative stress.
Methods
We screened for oxidative stress-related lncRNAs that could improve melanoma patient prognosis using the TCGA and GTEx databases. Utilizing differentially expressed oxidative stress-related lncRNAs (DE-OSlncRNAs), we constructed a Lasso regression model. The accuracy of the model was validated using univariate and multivariate regression, Kaplan-Meier (K-M) curves, and ROC curves. Subsequently, we conducted immune infiltration analysis, immune checkpoint differential analysis, IC50 pharmaceutical analysis, and gene set enrichment analysis. Investigating the effects of the target gene on melanoma using fluorescence in situ hybridization (FISH), quantitative real-time PCR (qRT-PCR), Edu assay, wound healing assay, transwell assay, flow cytometry, and reactive oxygen species (ROS) detection.
Results
Thirteen lncRNAs were identified as significant prognostic factors. Four oxidative stress-related lncRNAs (COPDA1, LINC02132, LINC02812, and MIR205HG) were further validated by fluorescence in situ hybridization (FISH), with results consistent with our data analysis. LINC02132 and COPDA1 can influence the proliferation, invasion, migration, and apoptosis of melanoma.
Conclusion
Our findings suggest that upregulation of the LINC02132 or COPDA1 genes elevates intracellular reactive oxygen species (ROS) levels in melanoma cells, suppresses tumor cell proliferation, migration, and invasion, and promotes apoptosis. These results suggest a novel therapeutic strategy for melanoma treatment.
... Further analysis revealed that the active compound in this fraction is the prodigiosin analog, Streptorubin B. Subsequent SAR studies were then carried out on various prodigiosin analogs to investigate their interaction with Bcl-2. Among these analogs, a synthetic prodigiosin derivative named Obatoclax (OBX) was chemically prepared and proved to be an effective BH3mimetic molecule through preclinical studies [78][79][80] (Fig. 12). OBX has shown the ideal inhibition of Bcl-2. ...
The Prodiginins (PGs) natural pigments are secondary metabolites produced by a broad spectrum of gram-negative and gram-positive bacteria, notably by species within the Serratia and Streptomyces genera. These compounds exhibit diverse and potent biological activities, including anticancer, immunosuppressive, antimicrobial, antimalarial, and antiviral effects. Structurally, PGs share a common tripyrrolic core but possess variable side chains and undergo cyclization, resulting in structural diversity. Studies have investigated their antiproliferative effects on various cancer cell lines, with some PGs advancing to clinical trials for cancer treatment. This review aims to illuminate the molecular mechanisms underlying PG-induced apoptosis in cancer cells and explore the structure-activity relationships pertinent to their anticancer properties. Such insights may serve as a foundation for further research in anticancer drug development, potentially leading to the creation of novel, targeted therapies based on PGs or their derivatives.
... PG has shown strong anti-cancer effects, with proven efficacy in treating melanoma, breast cancer, lung cancer, lymphocytic leukemia, and glioblastoma (Pan et al., 2012;Brown et al., 2015;Cheng et al., 2018;Chiu et al., 2018;Espona-Fiedler et al., 2022). It triggers apoptosis in cancer cells, including multidrug-resistant ones, with minimal toxicity to normal cells (Elahian et al., 2013). ...
... Inhibiting tumor cell migration and motility is essential for achieving anti-cancer effects. Research by Margarita Espona-Fiedler and her team found that PGs effectively reduce the adhesive capability of melanoma cells, impeding their ability to colonize distant organs and preventing metastasis (Espona-Fiedler et al., 2022). PG treatment also decreases the adhesive capacity of metastatic lung cancer cells and reduces filopodia formation in melanoma cells, which are crucial for cancer cell migration and proliferation. ...
Prodigiosin (PG) is a red tripyrrole pigment from the prodiginine family that has attracted widespread attention due to its excellent biological activities, including anticancer, antibacterial and anti-algal activities. The synthesis and production of PG is of particular significance, as it has the potential to be utilized in a number of applications, including those pertaining to clinical drug development, food safety, and environmental management. This paper provides a systematic review of recent research on PG, covering aspects like chemical structure, bioactivity, biosynthesis, gene composition and regulation, and optimization of production conditions, with a particular focus on the biosynthesis and regulation of PG in Serratia marcescens. This provides a solid theoretical basis for the drug development and production of PG, and is expected to promote the further development of PG in medicine and other applications.
... Surgical intervention and chemotherapy, as the most common therapeutic methods, may be associated with different complications (Debela et al., 2021;Zeng et al., 2023). Despite the development of different therapy methods, metastatic tumors are mainly untreatable and are responsible for the preponderance of deaths due to cancer (Espona-Fiedler et al., 2023). A major barrier to the development of efficient therapies is the complexity of tumors. ...
Multipotent mesenchymal stem cells (MSCs) are widely accepted as a useful tool for cell-based therapy of various diseases including malignancies. The therapeutic effects of MSCs are mainly attributed to their immunomodulatory and immunosuppressive properties. Despite the promising outcomes of MSCs in cancer therapy, a growing body of evidence implies that MSCs also show tumorigenic properties in the tumor microenvironment (TME), which might lead to tumor induction and progression. Owing to the broad-spectrum applications of MSCs, this challenge needs to be tackled so that they can be safely utilized in clinical practice. Herein, we review the diverse activities of MSCs in TME and highlight the potential methods to convert their protumorigenic characteristics into onco-suppressive effects.
