Juglone-Bearing Thiopyrano[2,3-d]thiazoles Induce Apoptosis in Colorectal Adenocarcinoma Cells DOI Creative Commons
Yuliia Kozak, Nataliya Finiuk, Robert Czarnomysy

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(6), P. 465 - 465

Published: March 20, 2025

Colorectal cancer is a major global health challenge, with current treatments limited by toxicity and resistance. Thiazole derivatives, known for their bioactivity, are emerging as promising alternatives. Juglone (5-hydroxy-1,4-naphthoquinone) naturally occurring compound anticancer properties, its incorporation into thiopyrano[2,3-d]thiazole scaffolds may enhance therapeutic potential. This study examined the cytotoxicity of thiopyrano[2,3-d]thiazoles effects on apoptosis in colorectal cells. Les-6547 Les-6557 increased population ROS-positive HT-29 cells approximately 10-fold compared control (36.3% 38.5% vs. 3.8%, respectively), potentially contributing to various downstream effects. Elevated ROS levels were associated cell cycle arrest, inhibition DNA biosynthesis, reduced proliferation. A significant shift distribution was observed, an increase S-phase (from 17.3% 34.7% 51.3% Les-6557, respectively) G2/M phase 24.3% 39.9% 28.8%). Additionally, inhibited biosynthesis cells, IC50 values 2.21 µM 2.91 µM, respectively. generation initiate intrinsic apoptotic pathway. activated both extrinsic pathways, demonstrated notable increases activity caspase 3/7, 8, 9, 10. provides robust basis investigating detailed molecular mechanisms action potential Les-6557.

Language: Английский

PLD1 is a key player in cancer stemness and chemoresistance: Therapeutic targeting of cross-talk between the PI3K/Akt and Wnt/β-catenin pathways DOI Creative Commons

Seong Hun Lim,

Hyesung Lee, Hyun Ji Lee

et al.

Experimental & Molecular Medicine, Journal Year: 2024, Volume and Issue: 56(7), P. 1479 - 1487

Published: July 1, 2024

Abstract The development of chemoresistance is a major challenge in the treatment several types cancers clinical settings. Stemness and are chief causes poor outcomes. In this context, we hypothesized that understanding signaling pathways responsible for crucial novel targeted therapies to overcome drug resistance. Among aberrantly activated pathways, PI3K-Akt/Wnt/β-catenin pathway clinically implicated malignancies such as colorectal cancer (CRC) glioblastoma multiforme (GBM). Aberrant dysregulation phospholipase D (PLD) has been malignancies, oncogenic activation facilitates tumor proliferation, stemness, chemoresistance. Crosstalk involving PLD Wnt/β-catenin promotes progression CRC GBM reduces sensitivity cells standard therapies. Notably, both tightly regulated connected at multiple levels by upstream downstream effectors. Thus, gaining deeper insights into interactions between these would help researchers discover unique therapeutic targets management drug-resistant cancers. Here, review molecular mechanisms which stimulates stemness GBM. current aims address importance central player coordinating cross-talk PI3K/Akt proposes possibility targeting improve therapy

Language: Английский

Citations

3
Adaptive Plasticity Tumor Cells Modulate MAPK-Targeting Therapy Response in Colorectal Cancer DOI Open Access
Oscar E. Villarreal, Yixin Xu, Ha Tran

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 24, 2025

Abstract MAPK pathway inhibitors (MAPKi) are increasingly used in the treatment of advanced colorectal cancer, but often produce short-lived responses patients. Although acquired resistance by de novo mutations tumors have been found to reduce response some patients, additional mechanisms underlying limited durability targeting therapy remain unknown. Here, we denote new contributory tumor biology and provide insight on impact plasticity response. Analysis MAPKi treated patients revealed activation stemness programs increased ASCL2 expression, which associated with poor outcomes. Greater was also seen patient-derived CRC models, independent driver mutations. We find denotes a distinct cell population, arising from phenotypic plasticity, proliferative, stem-like phenotype, decreased sensitivity therapy, were named adaptive (APT) cells. suppression induces APT phenotype cells, resulting enrichment limiting preclinical clinical data. depletion improved efficacy extended mice. These findings uncover cellular program that mitigates therapies highlights importance addressing improve

Language: Английский

Citations

0
Innovative Therapeutic Approach Targeting Colon Cancer Stem Cells: Transitional Cold Atmospheric Plasma DOI Creative Commons
Abolfazl Soulat, Taghi Mohsenpour, Leila Roshangar

et al.

ACS Omega, Journal Year: 2025, Volume and Issue: 10(12), P. 12109 - 12121

Published: March 6, 2025

Transitional cold atmospheric plasma (TCAP) represents a novel technique for generating remotely from primary source. It consists of partially nonthermal ionized gas mixture containing charged and neutral particles, photons, free radicals. In recent years, TCAP has attracted considerable attention in biomedical applications. order to evaluate colon cancer stem cells' (CCSCs) proliferation, apoptotic induction, inflammatory response, survival, was utilized both directly indirectly this study. Using argon helium gases, continuously delivered two stages during the experiment. For direct state, irradiated onto CCSCs 3 5 min. indirect technique, Matrigel treated with min before introduction cells. vitro assays demonstrated that exposure significantly reduced viability CCSCs; application had greater impacts than argon. Numerous investigations confirmed induction apoptosis, showing groups more cells altered cellular structures controls (****p < 0.0001). A substantial increase Bax/Bcl-2 ratio found by analyzing expression Bax Bcl-2 genes, indicating increased susceptibility apoptosis (*p = 0.0177 ***p 0.0004). The higher efficacy mode further highlighted marker analysis, which showed significant reduction interleukin-6 interleukin-8 TCAP-helium compared TCAP-argon (**p 0.0015 0.0007). Lastly, proliferation test, relies on Ki-67 expression, noteworthy decline all TCAP-treated groups, group exhibiting most robust impact 0.0014). Overall, findings highlight potential TCAP, particularly helium, as promising approach selectively targeting providing insights into its therapeutic mechanisms treatment. therefore, emerges unique strategy applications cell-targeted therapies.

Language: Английский

Citations

0
MiR-769-5p of macrophage exosomes induced by GRP78 promotes stemness and chemoresistance in colorectal cancer DOI Creative Commons
Jinmiao Tian, Lichao Zhang, Xiaoqin La

et al.

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 5, 2025

The tumor microenvironment (TME) plays an important role in tumorigenesis and development. Tumor-associated macrophages (TAMs) are essential members of the TME, exosomes miRNAs they secrete crucial regulation. Our previous study showed that GRP78-induced infinitely tend to be M2-type TAMs. In this study, M0 macrophage were collected co-incubated with colorectal cancer (CRC) cells. results implied induced by GRP78 (GRP78-exos) significantly promoted stemness chemoresistance CRC vitro vivo. Further, top 5 upregulated GRP78-exos obtained from miRNA sequencing data. qRT-PCR validation revealed miR-769-5p was most observably could directly transferred into cells via GRP78-exos. Mechanistically, indicated targeted MAPK1 regulate cell cycle-related proteins RB1, cyclin D1, E1. This contributes entering a quiescent state, which leads development chemoresistance. Moreover, is also expressed higher tissues 5-FU-resistant patients. summary, findings indicate novel function as potential marker for diagnosis treatment chemotherapy resistance CRC.

Language: Английский

Citations

0
Juglone-Bearing Thiopyrano[2,3-d]thiazoles Induce Apoptosis in Colorectal Adenocarcinoma Cells DOI Creative Commons
Yuliia Kozak, Nataliya Finiuk, Robert Czarnomysy

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(6), P. 465 - 465

Published: March 20, 2025

Colorectal cancer is a major global health challenge, with current treatments limited by toxicity and resistance. Thiazole derivatives, known for their bioactivity, are emerging as promising alternatives. Juglone (5-hydroxy-1,4-naphthoquinone) naturally occurring compound anticancer properties, its incorporation into thiopyrano[2,3-d]thiazole scaffolds may enhance therapeutic potential. This study examined the cytotoxicity of thiopyrano[2,3-d]thiazoles effects on apoptosis in colorectal cells. Les-6547 Les-6557 increased population ROS-positive HT-29 cells approximately 10-fold compared control (36.3% 38.5% vs. 3.8%, respectively), potentially contributing to various downstream effects. Elevated ROS levels were associated cell cycle arrest, inhibition DNA biosynthesis, reduced proliferation. A significant shift distribution was observed, an increase S-phase (from 17.3% 34.7% 51.3% Les-6557, respectively) G2/M phase 24.3% 39.9% 28.8%). Additionally, inhibited biosynthesis cells, IC50 values 2.21 µM 2.91 µM, respectively. generation initiate intrinsic apoptotic pathway. activated both extrinsic pathways, demonstrated notable increases activity caspase 3/7, 8, 9, 10. provides robust basis investigating detailed molecular mechanisms action potential Les-6557.

Language: Английский

Citations

0