Itraconazole inhibits the Hedgehog signaling pathway thereby inducing autophagy-mediated apoptosis of colon cancer cells.

Cell Death & Disease
Huiming DengRonghua Xu

Abstract

Itraconazole is as an antifungal medication used to treat systemic fungal infections. Recently, it has been reported to be effective in suppressing tumor growth by inhibiting the Hedgehog signaling pathway and angiogenesis. In the present study, we investigated whether itraconazole induces autophagy-mediated cell death of colon cancer cells through the Hedgehog signaling pathway. Cell apoptosis and cell cycle distribution of the colon cancer cell lines SW-480 and HCT-116 were detected by flow cytometry and terminal TUNEL assay. Autophagy and signal proteins were detected by western blotting and cell proliferation-associated antigen Ki-67 was measured using immunohistochemistry. The images of autophagy flux and formation of autophagosomes were observed by laser scanning confocal and/or transmission electron microscopy. Colon cancer cell xenograft mouse models were also established. Itraconazole treatment inhibited cell proliferation via G1 cell cycle arrest as well as autophagy-mediated apoptosis of SW-480 and HCT-116 colon cancer cells. In addition, the Hedgehog pathway was found to be involved in activation of itraconazole-mediated autophagy. After using the Hedgehog agonist recombinant human Sonic Hedgehog (rhshh), itraconazo...Continue Reading

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Aug 28, 2020·International Journal of Molecular Sciences·Taís Bacelar Sacramento de AraújoClarissa Araújo Gurgel Rocha
Aug 31, 2021·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Fei LiQing Zhang

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Methods Mentioned

BETA
surgical resection
electron microscopy
flow
Fluorescence
xenograft
xenografts
flow cytometry
transmission electron microscopy
confocal microscopy
confocal

Software Mentioned

ImageJ

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