RESUMEN
Colorectal cancer, the third most commonly occurring tumor worldwide, poses challenges owing to its high mortality rate and persistent drug resistance in metastatic cases. We investigated the tumor microenvironment, emphasizing the role of cancer-associated fibroblasts in the progression and chemoresistance of colorectal cancer. We used an indirect co-culture system comprising colorectal cancer organoids and cancer-associated fibroblasts to simulate the tumor microenvironment. Immunofluorescence staining validated the characteristics of both organoids and fibroblasts, showing high expression of epithelial cell markers (EPCAM), colon cancer markers (CK20), proliferation markers (KI67), and fibroblast markers (VIM, SMA). Transcriptome profiling was conducted after treatment with anticancer drugs, such as 5-fluorouracil and oxaliplatin, to identify chemoresistance-related genes. Changes in gene expression in the co-cultured colorectal cancer organoids following anticancer drug treatment, compared to monocultured organoids, particularly in pathways related to interferon-alpha/beta signaling and major histocompatibility complex class II protein complex assembly, were identified. These two gene groups potentially mediate drug resistance associated with JAK/STAT signaling. The interaction between colorectal cancer organoids and fibroblasts crucially modulates the expression of genes related to drug resistance. These findings suggest that the interaction between colorectal cancer organoids and fibroblasts significantly influences gene expression related to drug resistance, highlighting potential biomarkers and therapeutic targets for overcoming chemoresistance. Enhanced understanding of the interactions between cancer cells and their microenvironment can lead to advancements in personalized medical research..
RESUMEN
Algae are unique natural products that can produce various types of biologically active compounds. The 70% ethanol extract of brown algae Sargassum macrocarpum collected from the East Sea of Korea inhibited human monoamine oxidases A and B enzymes (hMAO-A and hMAO-B) at a 50 µg/mL concentration. The bioassay-guided isolation was performed through solid-phase extraction and the Sepbox system followed by serial high-performance liquid chromatography on the reverse phase condition, resulting in the identification of two new monocyclic terpenoid lactones, sargassumins A and B (1 and 2). The planar structures of the compounds were determined by a combination of spectroscopic data. The absolute configurations were determined by the interpretation of circular dichroism data. Compound 1 exhibited mild hMAO-A inhibition (42.18 ± 2.68% at 200 µM) and docked computationally into the active site of hMAO-A (-8.48 kcal/mol). Although compound 2 could not be tested due to insufficient quantity, it docked better into hMAO-A (-9.72 kcal/mol). Therefore, the above results suggest that this type of monocyclic terpenoid lactone could be one of the potential lead compounds for the treatment of psychiatric or neurological diseases.
RESUMEN
Gastrodia elata is widely used in traditional medicine and contains various types of metabolites with pharmacological activity. In the course of searching for neuroprotective molecules associated with the potential of G. elata in the treatment of neurodegenerative disorders, two new phenolic compounds (1 and 2) and a new tripeptide (3), together with 16 known compounds (4-19), were isolated from the rhizomes of G. elata. The structures of the compounds were determined by the interpretation of spectroscopic data, including nuclear magnetic resonance and mass spectrometry data. All obtained compounds were assessed for their ability to protect neuronal cells against neurotoxicity and neuroinflammation. Of these, 4 and 5 were found to possess moderate activities in HT22 hippocampal neuronal cells, whereas 2, 6, and 7 showed weak activities in R28 retinal cells. Additionally, compound 9 showed moderate inhibitory activity on lipopolysaccharide-induced nitric oxide production in BV2 microglial cells.