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Int J Mol Sci
2022 Apr 03;237:. doi: 10.3390/ijms23073991.
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Coriloxin Exerts Antitumor Effects in Human Lung Adenocarcinoma Cells.
Kuo YH
,
Wang YX
,
Peng WH
,
Chi NY
,
Lee TH
,
Wang CC
.
Abstract
Both in Taiwan and around the world, lung cancer is a primary cause of cancer-related deaths. In Taiwan, the most prevalent form of lung cancer is lung adenocarcinoma, a type of non-small-cell lung carcinoma. Although numerous lung cancer therapies are available, their clinical outcomes are unsatisfactory. Natural products, including fungal metabolites, are excellent sources of pharmaceutical compounds used in cancer treatment. We employed in vitro cell invasion, cell proliferation, cell migration, cell viability, and colony formation assays with the aim of evaluating the effects of coriloxin, isolated from fermented broths of Nectria balsamea YMJ94052402, on human lung adenocarcinoma CL1-5 and/or A549 cells. The potential targets regulated by coriloxin were examined through Western blot analysis. The cytotoxic effect of coriloxin was more efficiently exerted on lung adenocarcinoma cells than on bronchial epithelial cells. Moreover, low-concentration coriloxin significantly suppressed adenocarcinoma cells' proliferative, migratory, and clonogenic abilities. These inhibitory effects were achieved through ERK/AKT inactivation, epithelial-mesenchymal transition regulation, and HLJ1 expression. Our findings suggest that coriloxin can be used as a multitarget anticancer agent. Further investigations of the application of coriloxin as an adjuvant therapy in lung cancer treatment are warranted.
CMFJ10204 Chi-Mei Hospital, MOST 105-2320-B-030-006 Ministry of Science and Technology, Taiwan, MOST 107-2314-B-030-010-MY2 Ministry of Science and Technology, Taiwan
Figure 1. Influence of coriloxin on BEAS2B, A549, and CL1-5 cell viability. (A) Chemical composition of the isolated coriloxin. Following treatment with various concentrations of coriloxin, (B) BEAS2B, (C) A549, and (D) CL1-5 cells were subjected to the MTT assay. Results shown are percentages of the solvent control group (0.01% DMSO). These results are representative of two independent experiments performed, at least, in triplicate. Data are expressed as mean ±SD.
Figure 2. Antiproliferative effects of coriloxin on lung cancer cells. The proliferation activity of (A) A549 and (B) CL1-5 cells (n = 6 per group) treated with coriloxin for 24, 48, or 72 h was examined. Each experiment was performed, at least, in triplicate, and the values were reported as mean ± SD. * p < 0.05 indicates a significant difference from the solvent control group (0.01% DMSO).
Figure 3. Anticlonogenic effects of coriloxin on CL1-5 cells. Representative images and integrated results of cells (n = 4 per group) under the (A) anchorage-dependent and (B) anchorage-independent clonogenic assays are presented. The graphs summarize the analytical results. Values are reported as means ±SD (n ≥ 3). * p < 0.05 indicates a significant difference from the solvent control group (0.01% DMSO). Scale bars, 1 cm.
Figure 4. Antimigratory and anti-invasive effects of coriloxin on CL1-5 cells. (A) Wound-healing assay of the coriloxin-treated CL1-5 cells. We counted cells migrating into the wound area 4 and 8 h after wounding. (B) Cell invasion effects exerted by coriloxin (indicated concentrations). The data are representative of three independent experiments and are indicated as the mean ± SD. * p < 0.05 indicates a significant difference from the solvent control group (0.01% DMSO). (C) Gelatin zymography assay of MMP-2 and MMP-9 activities in coriloxin-treated cells.
Figure 5. Effects of coriloxin treatment on ERK/AKT and the expression of EMT-related proteins in CL1-5 cells, as determined through Western blot analysis. (A) Effects of coriloxin on p-ERK1/2, ERK2, p-AKT, and AKT levels. Cells were treated with 10 µM coriloxin or 0.01% DMSO (solvent control), after which Western blotting revealed the protein expression levels. (B) Protein levels of EMT-related genes (Vimentin, N-cad, and E-cad) in CL1-5 cells subjected to 48 h coriloxin treatment (at indicated concentrations). The solvent control group was exposed to 0.01% DMSO. The loading controls were GADPH or α-tubulin. Each experiment was performed, at least, in duplicate.
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