Sustainability of CD24 expression, cell proliferation and migration, cisplatin-resistance, and caspase-3 expression during mesenchymal-epithelial transition induced by the removal of TGF-β1 in A549 lung cancer cells

Kim, Seong‐Kwan; Park, Jina; Zhang, Dan; Cho, Sang Hyun; Yi, Hee; Cho, Soo‐Min; Chang, Byung-Joon; Kim, Jin-Suk; Shim, Jae-Han; El‐Aty, A. M. Abd; Shin, Ho‐Chul

doi:10.3892/ol.2017.6398

Cited by 8 publications

(9 citation statements)

References 31 publications

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“…Treating cells with different melatonin concentrations dependently reduced sphere formation (Figure A). Accumulating studies suggested that CD133 appeared to be a potential lung cancer stem cell marker . We also found that melatonin inhibits CD133 expression, according to data from the western blot and qPCR assay (Figure B).…”

Section: Resultssupporting

confidence: 68%

Melatonin reduces lung cancer stemness through inhibiting of PLC, ERK, p38, β‐catenin, and Twist pathways

Yang

Chiou

Chen³

et al. 2018

Environmental Toxicology

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Lung cancer is one of the most common cancer in cancer-related deaths worldwide, which is characterized by its strong metastatic potential. The melatonin hormone secreted by the pineal grand has an antioxidant effect and protects cells against carcinogenic substances. However, the effects of melatonin in lung cancer stemness are largely unknown. We found that melatonin reduces CD133 expression by~50% in lung cancer cell lines, while results of a sphere formation assay showed that melatonin inhibits lung cancer stemness. These effects of melatonin were reversed when the cell lines were incubated with phospholipase C (PLC), ERK/p38, and a β-catenin activator. Transfection with Twist siRNA augmented the inhibitory effects of melatonin, indicating that melatonin suppresses lung cancer stemness by inhibiting the PLC, ERK/p38, β-catenin, and Twist signaling pathways. We also found CD133 expression is positively correlated with Twist expression in lung cancer specimens. Melatonin shows promise in the treatment of lung cancer stemness and deserves further study. K E Y W O R D S lung cancer, melatonin, stemness, Twist 1 | INTRODUCTION Lung cancer is a major occasion of cancer mortality. Non-small cell lung cancer (NSCLC) is the most general type of lung cancer, accounting for more than 85% of all lung cancers. 1,2 Although chemotherapy and radiotherapy have improved lung cancer treatment over the past few decades, survival rates remain poor, with approximately 15% of patients remaining alive at 5 years after diagnosis. This poor prognosis is due to metastasis in the late stage of disease. Cells with a stem-like, dormant phenotype, endowed with unlimited self-renewal and high tumorigenic capability, are deemed responsible for post-therapy relapse and metastatic dissemination in various cancers, including lung cancer. 3-5 Therefore, the drugs that attack the cancer stem cells (CSCs) population have therapeutic benefit.Melatonin (N-acetyl-5-methoxytryptamine), a hormone secreted by the pineal grand and other organs, is produced in a circadian rhythm in reply to photic signaling from the retina. 6,7 Melatonin is important for controlling the immune system 8-10 and has an antioxidant effect. 11,12 This agent protects cells against carcinogenic substances and inhibits the development, metastasis, invasion and angiogenesis of many types

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Section: Resultssupporting

confidence: 68%

Melatonin reduces lung cancer stemness through inhibiting of PLC, ERK, p38, β‐catenin, and Twist pathways

Yang

Chiou

Chen³

et al. 2018

Environmental Toxicology

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“…While EMT most likely drives the escape of cancer cells from the primary tumor site, the reverse process, termed mesenchymal–epithelial transition (MET), is thought to drive the colonization at the distant metastatic site 40 , 41 . To explore whether the mesenchymal–epithelial plasticity affects the expression of ofCS on cancer cells, we removed TGF-β from the culture media of EMT-induced A549 cells 42 . Seventy-two hours after the removal of TGF-β, mesenchymal markers, such as fibronectin and N-cadherin, were reduced, indicating that the A549 cells had returned to a more epithelial state (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

The VAR2CSA malaria protein efficiently retrieves circulating tumor cells in an EpCAM-independent manner

et al. 2018

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Isolation of metastatic circulating tumor cells (CTCs) from cancer patients is of high value for disease monitoring and molecular characterization. Despite the development of many new CTC isolation platforms in the last decade, their isolation and detection has remained a challenge due to the lack of specific and sensitive markers. In this feasibility study, we present a method for CTC isolation based on the specific binding of the malaria rVAR2 protein to oncofetal chondroitin sulfate (ofCS). We show that rVAR2 efficiently captures CTCs from hepatic, lung, pancreatic, and prostate carcinoma patients with minimal contamination of peripheral blood mononuclear cells. Expression of ofCS is present on epithelial and mesenchymal cancer cells and is equally preserved during epithelial–mesenchymal transition of cancer cells. In 25 stage I–IV prostate cancer patient samples, CTC enumeration significantly correlates with disease stage. Lastly, rVAR2 targets a larger and more diverse population of CTCs compared to anti-EpCAM strategies.

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“…Combining chemotherapy drugs that act on different cell pathways could increase their individual effects against cell migration. Cisplatin can reduce A549 cell migration by acting through multiple pathways including those incorporating transforming growth factor β1 (TGF-β), Sox2, Wnt/β catenin signaling and the microRNA, miR-146a, through regulation of cyclin J [52,53,54]. However, the effect of cisplatin treatment against A549 migration can be mitigated by the development of resistance [52,55].…”

Section: Discussionmentioning

confidence: 99%

Anti-Cancer and Ototoxicity Characteristics of the Curcuminoids, CLEFMA and EF24, in Combination with Cisplatin

et al. 2019

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In this study, we investigated whether the curcuminoids, CLEFMA and EF24, improved cisplatin efficacy and reduced cisplatin ototoxicity. We used the lung cancer cell line, A549, to determine the effects of the curcuminoids and cisplatin on cell viability and several apoptotic signaling mechanisms. Cellular viability was measured using the MTT assay. A scratch assay was used to measure cell migration and fluorescent spectrophotometry to measure reactive oxygen species (ROS) production. Western blots and luminescence assays were used to measure the expression and activity of apoptosis-inducing factor (AIF), caspases-3/7, -8, -9, and -12, c-Jun N-terminal kinases (JNK), mitogen-activated protein kinase (MAPK), and proto-oncogene tyrosine-protein kinase (Src). A zebrafish model was used to evaluate auditory effects. Cisplatin, the curcuminoids, and their combinations had similar effects on cell viability (IC50 values: 2–16 μM) and AIF, caspase-12, JNK, MAPK, and Src expression, while caspase-3/7, -8, and -9 activity was unchanged or decreased. Cisplatin increased ROS yield (1.2-fold), and curcuminoid and combination treatments reduced ROS (0.75–0.85-fold). Combination treatments reduced A549 migration (0.51–0.53-fold). Both curcuminoids reduced auditory threshold shifts induced by cisplatin. In summary, cisplatin and the curcuminoids might cause cell death through AIF and caspase-12. The curcuminoids may potentiate cisplatin’s effect against A549 migration, but may counteract cisplatin’s effect to increase ROS production. The curcuminoids might also prevent cisplatin ototoxicity.

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Sustainability of CD24 expression, cell proliferation and migration, cisplatin-resistance, and caspase-3 expression during mesenchymal-epithelial transition induced by the removal of TGF-β1 in A549 lung cancer cells

Cited by 8 publications

References 31 publications

Melatonin reduces lung cancer stemness through inhibiting of PLC, ERK, p38, β‐catenin, and Twist pathways

Melatonin reduces lung cancer stemness through inhibiting of PLC, ERK, p38, β‐catenin, and Twist pathways

The VAR2CSA malaria protein efficiently retrieves circulating tumor cells in an EpCAM-independent manner

Anti-Cancer and Ototoxicity Characteristics of the Curcuminoids, CLEFMA and EF24, in Combination with Cisplatin

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