Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Chrysomycin a Regulates Proliferation and Apoptosis of Neuroglioma Cells via Akt/GSK-3β Signaling Pathway In Vivo and In Vitro

Version 1 : Received: 18 April 2023 / Approved: 19 April 2023 / Online: 19 April 2023 (08:00:29 CEST)

A peer-reviewed article of this Preprint also exists.

Liu, D.-N.; Liu, M.; Zhang, S.-S.; Shang, Y.-F.; Zhang, W.-F.; Song, F.-H.; Zhang, H.-W.; Du, G.-H.; Wang, Y.-H. Chrysomycin A Regulates Proliferation and Apoptosis of Neuroglioma Cells via the Akt/GSK-3β Signaling Pathway In Vivo and In Vitro. Mar. Drugs 2023, 21, 329. Liu, D.-N.; Liu, M.; Zhang, S.-S.; Shang, Y.-F.; Zhang, W.-F.; Song, F.-H.; Zhang, H.-W.; Du, G.-H.; Wang, Y.-H. Chrysomycin A Regulates Proliferation and Apoptosis of Neuroglioma Cells via the Akt/GSK-3β Signaling Pathway In Vivo and In Vitro. Mar. Drugs 2023, 21, 329.

Abstract

Glioblastoma (GBM) is a major type of primary brain tumors without ideal prognosis and it’s necessary to find novel compound possessing therapeutic effect. Chrysomycin A (Chr-A) has been reported to inhibit the proliferation, migration and invasion of U251 and U87-MG cells, but the mechanism of Chr-A against glioblastoma in vivo and whether Chr-A modulates apoptosis of neuroglioma cells is unclear.The present study was to elucidate the potential of Chr-A against glioblastoma in vivo and how Chr-A modulates apoptosis of neuroglioma cells. Briefly, The an-ti-glioblastoma activity was assessed in human glioma U87 xenografts nude mice. Chr-A-related targets were identified by RNA-seq. Apoptotic ratio and caspase 3/7 activity of U251 and U87-MG cells were assayed by flow cytometry. Apoptosis-related proteins and possible molecular mecha-nism were validated via Western blotting. The results showed that Chr-A treatment significantly inhibits glioblastoma progression in xenografts nude mice, and enrichment analysis suggested that apoptosis, PI3K-Akt and Wnt signaling pathway were involved in the possible mechanism. Chr-A increased apoptotic ratio and the activity of caspase 3/7 in U251 and U87-MG cells. Western blot revealed that Chr-A broke the balance between Bax and Bcl-2 activating caspase cascade re-action and downregulated the expression of p-Akt and p-GSK-3β, suggesting that Chr-A may contribute to glioblastoma regression modulating Akt/GSK-3β signaling pathway to promote apoptosis of neuroglioma cells in vivo and in vitro. Therefore, Chr-A may hold therapeutic promise for glioblastoma.

Keywords

Chrysomycin A; Xenograft mouse model; Glioblastoma; Apoptosis

Subject

Medicine and Pharmacology, Medicine and Pharmacology

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