Acridine Yellow G Blocks Glioblastoma Growth via Dual Inhibition of Epidermal Growth Factor Receptor and Protein Kinase C Kinases

Qi, Qi; He, Kunyan; Yoo, Min-Heui; Chan, Chi Bun; Liu, Xia; Zhang, Zhaobin; Olson, Jeffrey J.; Xiao, Gui; Wang, Liya; Mao, Hui; Fu, Haian; Tao, Hui; Ramalingam, Suresh S.; Sun, Shi-Yong; Mischel, Paul S.; Ye, Keqiang

doi:10.1074/jbc.m111.293605

Cited by 9 publications

(11 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The anti-apoptotic Bcl-2 protein helps to block apoptosis cascade by preventing the release of mitochondrial apoptogenic factors, presumably via interaction with the mitochondrial porin channel [25]. Bax, proapoptotic protein, is responsible for the release of mitochondrial intermembrane space proteins, such as cytochrome c, Smac/Diablo, EndoG, Omi/HtrA2 and AIF [11,16]. The ratio Bax/Bcl-2 have been demonstrated as an indicator of apoptosis and regulation of the ratio is one of the mechanisms involving apoptosis induction [26,27].…”

Section: Discussionmentioning

confidence: 99%

“…After 24, 48, and 72 hours of incubation, the culture medium was removed and the cells washed twice with PBS. MTT assay was carried out as described with little modification [11]. Then 0.5 mg/ml MTT solution was added to each well.…”

Section: Methodsmentioning

confidence: 99%

“…Body weight was determined at the end of experiment and tumors were measured every three days after the initiation of treatment. Tumor volumes were determined by measuring two perpendicular diameters using callipers; the volume was then determined using the formula (length × width 2 ) / 2, where length was the longest axis and width being the measurement at right angles to the length [11].…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Noscapine inhibits human hepatocellular carcinoma growth through inducing apoptosis in vitro and in vivo

Xu¹,

Z²,

Dong³

et al. 2016

neo

View full text Add to dashboard Cite

Noscapine, a phthalideisoquinoline alkaloid derived from opium, has been demonstrated as a promising anti-tumor compound against various cancers. However, the anti-cancer activity of noscapine in hepatocellular carcinoma has not been defined. In this study, we investigate the inhibitive effects of noscapine on human hepatocellular carcinoma (HCC) using both in vitro and in vivo models. In vitro proliferation assay showed that noscapine suppressed HepG2 and Huh7 cells in dose- and time-dependent manners. With a mouse xenograft model, noscapine showed notable inhibition on HCC tumor growth in vivo without suppression of body weight. Moreover, apoptotic induction and regulation of related signalings by noscapine were examined by nuclear DNA staining, TUNEL, and western blotting assays. Results showed that noscapine induced apoptosis in HCC cells both in vitro and in vivo. Further studies indicated that noscapine induced antive-capsase-3, cleavage PARP, and decreased the ratio of Bcl-2/Bax. Hence, these data indicates that noscapine selectively suppresses HCC cell growth through apoptosis induction, providing evidence for application of noscapine as a novel agent against human hepatocellular carcinoma.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Noscapine inhibits human hepatocellular carcinoma growth through inducing apoptosis in vitro and in vivo

Xu¹,

Z²,

Dong³

et al. 2016

neo

View full text Add to dashboard Cite

show abstract

“…When tested in U87MG cell lines, acridine yellow G directly inhibits the kinases EGFR and PKCs with IC50 values of ∼7.5 and 5 μM, respectively, consequentially blocking the mTOR signaling and triggering the cell cycle arrest in the G 1 phase, and, in turn, activating the apoptotic process in tumors. In particular, acridine yellow G preferentially blocks cell proliferation of the most malignant U87MG/EGFRvIII cells (PTEN-deficient U87MG glioblastoma cells that overexpress EGFRvIII) over the less malignant PTEN stably transfected U87MG cells ( Qi et al, 2012 ). In vivo studies indicated that Acridine yellow G has the ability to induce a reduction of the tumor volumes in both subcutaneous and intracranial mice models.…”

Section: The Multi-targeted Strategymentioning

confidence: 99%

“…Toxic effects in animals subjected to chronic treatment were undetectable. Globally, results indicate that Acridine yellow G is a safe and effective therapeutic agent for the treatment of aggressive gliomas, as well as other types of human cancers, such as lung cancer, that are also inhibited by this compound ( Qi et al, 2012 ).…”

Section: The Multi-targeted Strategymentioning

confidence: 99%

New Multitarget Approaches in the War Against Glioblastoma: A Mini-Perspective

et al. 2018

View full text Add to dashboard Cite

Glioblastoma multiforme (GBM) is the most common tumor of the CNS, and the deadliest form of brain cancer. The rapid progression, the anatomic location in the brain and a deficient knowledge of the pathophysiology, often limit the effectiveness of therapeutic interventions. Current pillars of GBM therapies include surgical resection, radiotherapy and chemotherapy, but the low survival rate and the short life expectation following these treatments strongly underline the urgency to identify innovative and more effective therapeutic tools. Frequently, patients subjected to a mono-target therapy, such as Temozolomide (TMZ), develop drug resistance and undergo relapse, indicating that targeting a single cellular node is not sufficient for eradication of this disease. In this context, a multi-targeted therapeutic approach aimed at using compounds, alone or in combination, capable of inhibiting more than one specific molecular target, offers a promising alternative. Such strategies have already been well integrated into drug discovery campaigns, including in the field of anticancer drugs. In this miniperspective, we will discuss the recent progress in the treatment of GBM focusing on innovative and effective preclinical strategies, which are based on a multi-targeted approach.

show abstract

Targeted Delivery of DNA Topoisomerase Inhibitor SN38 to Intracranial Tumors of Glioblastoma Using Sub‐5 Ultrafine Iron Oxide Nanoparticles

Xie

Jones

et al. 2022

Adv Healthcare Materials

Self Cite

View full text Add to dashboard Cite

Effectively delivering therapeutics for treating brain tumors is hindered by the physical and biological barriers in the brain. Even with the compromised blood–brain barrier and highly angiogenic blood–tumor barrier seen in glioblastoma (GBM), most drugs, including nanomaterial‐based formulations, hardly reach intracranial tumors. This work investigates sub‐5 nm ultrafine iron oxide nanoparticles (uIONP) with 3.5 nm core diameter as a carrier for delivering DNA topoisomerase inhibitor 7‐ethyl‐10‐hydroxyl camptothecin (SN38) to treat GBM. Given a higher surface‐to‐volume ratio, uIONP shows one‐ or three‐folds higher SN38 loading efficiency (48.3 ± 6.1%, mg/mg Fe) than those with core sizes of 10 or 20 nm. SN38 encapsulated in the coating polymer exhibits pH sensitive release with <10% over 48 h at pH 7.4, but 86% at pH 5, thus being protected from converting to inactive glucuronide by UDP‐glucuronosyltransferase 1A1. Conjugating αvβ3‐integrin‐targeted cyclo(Arg‐Gly‐Asp‐D‐Phe‐Cys) (RGD) as ligands, RGD‐uIONP/SN38 demonstrates targeted cytotoxicity to αvβ3‐integrin‐overexpressed U87MG GBM cells with a half‐maximal inhibitory concentration (IC50) of 30.9 ± 2.2 nm. The efficacy study using an orthotopic mouse model of GBM reveals tumor‐specific delivery of 11.5% injected RGD‐uIONP/SN38 (10 mg Fe kg−1), significantly prolonging the survival in mice by 41%, comparing to those treated with SN38 alone (p < 0.001).

show abstract

Acridine Yellow G Blocks Glioblastoma Growth via Dual Inhibition of Epidermal Growth Factor Receptor and Protein Kinase C Kinases

Cited by 9 publications

References 35 publications

Noscapine inhibits human hepatocellular carcinoma growth through inducing apoptosis in vitro and in vivo

Noscapine inhibits human hepatocellular carcinoma growth through inducing apoptosis in vitro and in vivo

New Multitarget Approaches in the War Against Glioblastoma: A Mini-Perspective

Targeted Delivery of DNA Topoisomerase Inhibitor SN38 to Intracranial Tumors of Glioblastoma Using Sub‐5 Ultrafine Iron Oxide Nanoparticles

Contact Info

Product

Resources

About