Quinalizarin Triggers U251 Glioma Cell Apoptosis by Inhibiting Phosphatidylinositol 3-Kinase/Protein Kinase B/Mammalian Target of Rapamycin Signaling Pathway.

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Authors: Yunfeng Xu and Lingyuan Wu
Date: Nov. 2021
Publisher: New Century Health Publishers, LLC
Document Type: Article
Length: 4,760 words
Lexile Measure: 1460L

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Abstract :

We have explored whether quinalizarin could trigger human U251 glioma cell mortality and the mechanism(s) therein. Quinalizarin in a dose- and time-dependent manner activated caspase-3 and reduced cyclin-D1 activity in human 251 glioma cells. We observed that quinalizarin downregulated PI3K/Akt/mTOR signaling cascade that further resulted in stimulation of caspase-3 and suppression of the PI3K/Akt signaling cascade. These findings also revealed an increased caspase-3 activation, release of lactic dehydrogenase, and breakdown of Poly (ADP-ribose) polymerase with SH-6 [(2R)-2-methoxy-3-octadecoxypropyl] (2,3,4-trihydroxycyclohexyl) hydrogen phosphate, which is a protein kinase B inhibitor. Co-treatment with quinalizarin and LY294002/SH-6 exhibited enhanced glioma cell apoptosis. Overall the findings advocate protective effect of quinalizarin in U251 glioma cells via inhibition of the PI3K/Akt/mTOR signaling cascade. Keywords: Apoptosis, Glioma, NF-[KAPPA]B, PI3K/Akt/mTOR signaling, Quinalizarin, U251 cells Abbreviations Used: Protein kinase B, AKT; Bicinchoninic acid, BCA; B-cell lymphoma 2 protein, Bcl-2; B-cell lymphoma-extra-large, Bcl-xL; Ac-Asp-Glu-Val-Asp-pNA- a caspase-3 substrate, DEVD-p-NA; Dimethyl sulfoxide, DMSO; Epidermal growth factor, EGF; Epidermal growth factor receptor EGFR; 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid, HEPES; Lactic dehydrogenase, LDH; Mitogen-activated protein kinase, MAPK; Mammalian target of rapamycin, mTOR; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, MTT; Nuclear factor-kappa B, NF-[KAPPA]B; Cellular tumor antigen P53, P53; Poly (ADP-ribose) polymerase, PARP; Phosphatidylinositol 3-kinase, PI3K; Phosphatidylinositol-4,5-bisphosphate 3-kinase, PI3KCB; Phospho-mTOR, p-mTOR; p-nitroaniline, pNA; Phosphatase and tensin homolog, PTEN; Quinalizarin, QZ; Rapamycin, Rapa; Reactive oxygen species, ROS; [(2R)-2-methoxy-3-octadecoxypropyl] (2,3,4-trihydroxycyclohexyl) hydrogen phosphate-a protein kinase B inhibitor, SH-6; Small or short interfering RNA, siRNA; Transforming growth factor-[beta], TGF-[beta]

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Gale Document Number: GALE|A670225509