Microcystin‑leucine arginine promotes colorectal cancer cell proliferation by activating the PI3K/Akt/Wnt/β‑catenin pathway

Abstract

Microcystin-leucine arginine (MC-LR) is an environmental toxin produced by cyanobacteria and is considered to be a potent carcinogen. However, to the best of our knowledge, the effect of MC-LR on colorectal cancer (CRC) cell proliferation has never been studied. The aim of the present study was to investigate the effect of MC-LR on CRC cell proliferation and the underlying mechanisms. Firstly, a Cell Counting Kit-8 (CCK-8) assay was conducted to determine cell viability at different concentrations, and 50 nM MC-LR was chosen for further study.

Microcystin-leucine arginine induces the proliferation of cholangiocytes and cholangiocarcinoma cells through the activation of the Wnt/β-catenin signaling pathway

“…3 D). These findings align with prior research demonstrating that β-catenin and its downstream molecules, including Cyclin D1, are upregulated in colorectal cancer cells treated with MC-LR [ 23 ]. Increased levels of Cyclin D1 and β-catenin proteins have been linked to unfavorable survival outcomes in cancer patients, and Cyclin D1 is known to play crucial roles in cancer development and progression [ 65 , 66 ].…”

“…The concentrations of MC-LR employed in our study are comparable to those found in microcystin-polluted surface waters, typically below 100 μg/L (equivalent to approximately 100.5 nM) [ 29 ]. MC-LR is recognized for its dual impact on cells, eliciting cell death at high concentrations (>10 μM) [ 48 , 49 ] and promoting cell proliferation at lower concentrations (<500 nM) [ 23 , 30 , 32 ]. In our study, we found that 10 nM and 100 nM MC-LR stimulated cell division and migration in CCA and cholangiocytes cells at certain concentrations (10 nM and 100 nM) but not at lower (1 nM) or higher (1000 nM) concentrations.…”

“…To obtain 1, 10, 100, and 1000 nM of MC-LR for each experiment, the concentrate solution was diluted with the completed DMEM medium. These concentrations of MC-LR for treatment groups were selected based on microcystin-polluted surface waters, typically below 100 μg/L (equivalent to approximately 100.5 nM) [ 29 ], as well as many previous studies [ 23 , [30] , [31] , [32] ] that have utilized this concentration range.…”

“…A worse prognosis for CCA patients and the occurrence of multidrug resistance are related to increased β-catenin expression [ 22 ]. A previous report has shown that MC-LR could promote colon cancer growth through Wnt/β-catenin signaling pathway [ 23 ].…”

MicroRNA-203a inhibits breast cancer progression through the PI3K/Akt and Wnt pathways

“…Consequently, β-Catenin is unable to translocate to the nucleus and stimulate the expression of downstream target genes involved in cancerous phenotypes. The PI3K/Akt and Wnt/β-Catenin pathways are activated in several types of cancers 33 . The abnormal activation of the Akt/GSK3β/β-Catenin signaling pathway plays a key role in cancerous progress 34 , 35 .…”