GPD1L Suppresses Colon Adenocarcinoma Via Repressing TGFβ1/EMT

Colon adenocarcinoma is one of the most prevalent malignant tumors in human beings. Hence, the identification of valuable biomarkers and therapeutic targets is vital for improved treatment and patient outcomes. The role of glycerol-3-phosphate dehydrogenase 1-like (GPD1L) in several tumors has been achieved in recent years. However, the underlying mechanisms of GPD1L in colon adenocarcinoma remain elusive. In this study, we identified that GPD1L was associated with better prognosis in colon adenocarcinoma patients using gene expression omnibus (GEO) and the cancer genome atlas (TCGA) database. In addition, knockdown of GPD1L promoted the proliferation, migration and invasion and reversed by re-expression GPD1L in colon adenocarcinoma cells in vitro. According to gene set enrichment analysis (GSEA), GPD1L is closely correlated with transforming growth factor-β (TGFβ) signaling pathway in colon adenocarcinoma. Moreover, GPD1L downregulates epithelial mesenchymal transition (EMT) marker proteins via TGFβ1 due to Western blot analysis. These findings demonstrate that GPD1L inhibits the growth of colon adenocarcinoma cells by inhibiting EMT induced by TGFβ1. GPD1L may be a promising molecular target for the treatment of colon adenocarcinoma patients.

New Hybrids Based on Curcumin and Resveratrol: Synthesis, Cytotoxicity and Antiproliferative Activity against Colorectal Cancer Cells

We synthesized twelve hybrids based on curcumin and resveratrol, and their structures were elucidated by spectroscopic analysis. The chemopreventive potential of these compounds was evaluated against SW480 human colon adenocarcinoma cells, its metastatic derivative SW620, along with the non-malignant CHO-K1 cell line. Among the tested compounds, hybrids 3e and 3i (for SW480) and 3a, 3e and 3k (for SW620) displayed the best cytotoxic activity with IC50 values ranging from 11.52 ± 2.78 to 29.33 ± 4.73 µM for both cell lines, with selectivity indices (SI) higher than 1, after 48 h of treatment. Selectivity indices were even higher than those reported for the reference drug, 5-fluorouracil (SI = 0.96), the starting compound resveratrol (SI = 0.45) and the equimolar mixture of curcumin plus resveratrol (SI = 0.77). The previous hybrids showed good antiproliferative activity.

Adsorption of Phenazines Produced by Pseudomonas aeruginosa Using AST-120 Decreases Pyocyanin-Associated Cytotoxicity

AST-120 (Kremezin) is used to treat progressive chronic kidney disease by adsorbing uremic toxin precursors produced by the gut microbiota, such as indole and phenols. Previously, we found that AST-120 decreased drug tolerance and virulence in Escherichia coli by adsorbing indole. Here, we show that AST-120 adsorbs phenazine compounds, such as pyocyanin, produced by Pseudomonas aeruginosa including multidrug-resistant P. aeruginosa strains, and suppresses pyocyanin-associated toxicity in A-549 (alveolar adenocarcinoma) and Caco-2 (colon adenocarcinoma) cells. Addition of fosfomycin, colistin and amikacin, which are often used to treat P. aeruginosa, inhibited the bacterial growth, regardless of the presence or absence of AST-120. These results suggest a further benefit of AST-120 that supports anti-Pseudomonas chemotherapy in addition to that of E. coli and propose a novel method to treat P. aeruginosa infection.

The Presence of a Cyclohexyldiamine Moiety Confers Cytotoxicity to Pentacyclic Triterpenoids

Pentacyclic triterpenoids oleanolic acid, ursolic acid, betulinic acid, and platanic acid were acetylated and converted into several amides 9–31; the cytotoxicity of which has been determined in sulforhodamine B assays employing seral human tumor cell lines and nonmalignant fibroblasts. Thereby, a betulinic acid/trans-1,4-cyclohexyldiamine amide showed excellent cytotoxicity (for example, EC50 = 0.6 μM for HT29 colon adenocarcinoma cells).