An important clinical task is to coherently integrate the use of protein-targeted drugs into preexisting therapeutic regimens, with the goal of improving treatment efficacy. Constitutive activation of Ras-dependent signaling is important in many tumors, and agents that inhibit this pathway might be useful in numerous therapeutic combinations. The MCP compounds were identified as inhibitors of Ras-Raf interactions and previously shown to inhibit multiple Ras-dependent transformation phenotypes when used as monoagents in cell culture analyses. In this study, we investigate the ability of the MCP110 compound to synergistically enhance the activity of other therapeutic agents. In both a defined K-Ras-transformed fibroblast model and in human tumor cell lines with mutationally activated Ras, MCP110 selectively synergizes with other agents targeting the mitogen-activated protein kinase pathway, and with multiple agents (paclitaxel, docetaxel, and vincristine) targeting the microtubule network. The synergistic activity of MCP110 and paclitaxel was further established by experiments showing that in Kaposi's sarcoma oncogenically transformed cell lines, cellular models for tumors treated with taxanes in the clinic and in which Raf-dependent signaling plays an important role, MCP110 synergizes with paclitaxel and limit growth. Finally, in vivo testing indicate that MCP110 is bioavailable, inhibits the growth of LXFA 629 lung and SW620 colon carcinoma cells in xenograft models, and again strongly synergizes with paclitaxel. Together, these findings indicate that MCP compounds have potential to be effective in combination with other anticancer agents.
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http://dx.doi.org/10.1158/1535-7163.MCT-06-0602 | DOI Listing |
Life Sci
December 2024
Department of Pharmacology, Key Laboratory of Chemical Biology, Ministry of Education, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, PR China. Electronic address:
Aims: This study aims to investigate the role of SOD3 in gastric cancer (GC) progression and its impact on chemotherapy efficacy and toxicity. It further seeks to evaluate the therapeutic potential of MCP in enhancing SOD3 activity to improve treatment outcomes and reduce chemotherapy-induced peripheral neurotoxicity (CIPN).
Materials And Methods: We used overexpression plasmids and small interfering RNAs (siRNAs) to modulate the expression of SOD3 and Desmocollin2 (DSC2) in gastric cancer cells.
Int J Pharm
December 2024
Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, University of Barcelona, 08028 Barcelona, Spain; Institute of Nanoscience and Nanotechnology (IN(2)UB), University of Barcelona, 08028 Barcelona, Spain. Electronic address:
Ocular inflammation is a complex pathology with limited treatment options. While traditional therapies have side effects, novel approaches, such as natural compounds like Apigenin (APG) and Melatonin (MEL) offer promising solutions. APG and MEL, in combination with nanostructured lipid carriers (NLC), may provide a synergistic effect in treating ocular inflammation, potentially improving patient outcomes and reducing adverse effects.
View Article and Find Full Text PDFMol Cell Proteomics
December 2024
Biological Chemistry Department, David Geffen School of Medicine, UCLA, Los Angeles, CA, 90095, USA; Department of Chemistry and Biochemistry, UCLA, Los Angeles, CA, 90095, USA; Molecular Biology Institute, UCLA, Los Angeles, CA, 90095, USA; DOE Institute for Genomics and Proteomics, UCLA, Los Angeles, CA, 90095, USA; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA, 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, CA, 90095, USA. Electronic address:
Cysteine chemoproteomic screening platforms are widely utilized for chemical probe and drug discovery campaigns. Chemoproteomic compound screens, which use a mass spectrometry-based proteomic readout, can interrogate the structure activity relationship (SAR) for thousands of proteins in parallel across the proteome. The versatility of chemoproteomic screens has been demonstrated across electrophilic, nucleophilic, and reversible classes of molecules.
View Article and Find Full Text PDFJ Sci Food Agric
December 2024
Department of Plant Science, Postharvest Research Center, Federal University of Santa Maria, Santa Maria, Brazil.
Background: The present study investigated the effects of high CO partial pressures (pCO) in dynamic controlled atmosphere monitored by respiratory quotient (DCA-RQ 1.3) on the anaerobic metabolism compounds, physiological disorders and overall quality of 'Maxi Gala' apples after 9 months of storage (2.0 °C), plus 7 days of shelf life (20 °C).
View Article and Find Full Text PDFEcotoxicol Environ Saf
December 2024
Institute of Traditional Medicine and Bioscience, Daejeon University, Daejeon 34520, Republic of Korea. Electronic address:
Particulate matter (PM, diameter < 10 μm) and Diesel exhaust particles (DEP) exposure can cause severe respiratory disorders. This investigation explored the protective effects of Reliea® (RelA), combination of Codonopsis lanceolata and Chaenomeles sinensis extract, against airway inflammation related to PMD exposure. RelA treatment suppressed reactive oxygen species, nitric oxide release, cytokine expression (IL-6, IL-1β, iNOS, CXCL-2, MCP-1, and TNF-α), and the related inflammatory mechanisms in PM-induced alveolar macrophage cells.
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