Itraconazole Alters the Stem Cell Characteristics of A549 and NCI-H460 Human Lung Cancer Cells by Suppressing Wnt Signaling

Abstract

BackgroundCancer stem cells (CSCs) behave as their malignant counterparts, but persist after treatment, and possess properties that allow them to interact with their environment. Itraconazole, an antifungal agent, also has a role in suppressing tumor progression, but its effects in regulating tumor cell stemness remain unclear. This study aimed to evaluate the effects of itraconazole on A549 and NCI-H460 human lung cancer cell stemness in vitro.Material/MethodsA549 and NCI-H460 human lung cancer cells and BEAS-2B normal bronchial epithelial cells were cultured with and without itraconazole. Cell viability was evaluated. The expression of stem cell markers, CD133, ATP binding cassette subfamily G member 2 (ABCG2), and aldehyde dehydrogenase 1 (ALDH1), were measured by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR). Sphere-forming cells were evaluated in vitro.ResultsItraconazole reduced the expression of stemness molecules CD133, ABCG2, and ALDH1 in A549 and NCI-H460 human lung cancer cells, and the numbers of sphere-forming cells were reduced. However, itraconazole had little effect on cell viability but enhanced the chemosensitivity of A549 and NCI-H460 cells. Itraconazole inhibited Wnt signaling. Re-activation of Wnt signaling restored itraconazole-mediated inhibition on A549 and NCI-H460 cell stemness.ConclusionsItraconazole altered the stemness characteristics of A549 and NCI-H460 human lung cancer cells by suppressing Wnt signaling but did not affect cell viability.

Itraconazole attenuates the stemness of nasopharyngeal carcinoma cells via triggering ferroptosis

“…Additionally, itraconazole indeed could partially reverse the radiation resistance of NPC spheroids. Consistently, a recent work showed that itraconazole attenuates the stemness of lung cancer cells 21 . However, it is still unclear whether itraconazole holds the similar effects on other tumor cell stemness.…”

“…Consistently, a recent work showed that itraconazole attenuates the stemness of lung cancer cells. 21 However, it is still unclear whether itraconazole holds the similar effects on other tumor cell stemness. Notably, antifungal infection is an important implication during hematopoietic stem cell transplantation 27 and CSC shares the similar characteristics with the normal stem cells 28 ; thus, future work should be focused on whether itraconazole has the similar effects on normal stem cells.…”

“…Additionally, mouse organoid drug screening identifies that itraconazole generates spheroid collapse and loss of dormancy, and human colorectal cancer cell dormancy and tumor growth can also be perturbed by itraconazole by inhibiting Wnt signaling through noncanonical hedgehog signaling 20 . Notably, a recent study showed that itraconazole can perturb the stemness of human lung cancer cells and CSCs are normally in dormancy 21,22 . However, the roles of itraconazole in NPC progression are still unclear.…”

“…20 Notably, a recent study showed that itraconazole can perturb the stemness of human lung cancer cells and CSCs are normally in dormancy. 21,22 However, the roles of itraconazole in NPC progression are still unclear. Based on these above results, we assume that itraconazole can attenuate the stemness of NPC cells.…”

Effects of Diesel Exhaust Particles on Mouse Gastric Stem Cells

“…To test whether the cellular and molecular effects observed for DEPs are specific for mGS cells, we used another type of cells, lung epithelial A549 cell line that have some characteristics of stem/progenitor cells [30]. We first examined their morphology following incubation with 1, 10, and 100 µg/mL DEPs.…”