A novel drug conjugate, NEO212, targeting proneural and mesenchymal subtypes of patient-derived glioma cancer stem cells

Jhaveri, Niyati; Agasse, Fabienne; Armstrong, Don; Peng, Lilei; Commins, Deborah; Rosenstein-Sisson, Rachel; Vaikari, Vijaya Pooja; Santiago, Shayane; Santos, Tiago; Chen, Ligang; Schönthal, Axel H.; Chen, Thomas C.; Hofman, Florence M.

doi:10.1016/j.canlet.2015.11.040

Cited by 25 publications

(46 citation statements)

References 35 publications

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“…Human patient-derived glioma cells were isolated from freshly resected GBM tissues obtained according to the University of Southern California (USC, Los Angeles, CA) Institutional Review Board guidelines. Information regarding the detailed protocol and culture medium has been previously published (23). Patient-derived glioma cells were cultured in cancer stem cell culture (CSC) medium containing DMEM-F12 medium (Life Technologies) with 1% penicillin-streptomycin, 1% B-27 (Life Technologies), and 20 ng/mL EGF and bFGF (PeproTech).…”

Section: Cells and Reagentsmentioning

confidence: 99%

The Rolipram–Perillyl Alcohol Conjugate (NEO214) Is A Mediator of Cell Death through the Death Receptor Pathway

Cho

Thein

Swenson

et al. 2019

Molecular Cancer Therapeutics

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Glioblastoma (GBM) is a highly aggressive primary brain tumor with a poor prognosis. Treatment with temozolomide, standard of care for gliomas, usually results in drug resistance and tumor recurrence. Therefore, there is a great need for drugs that target GBM. NEO214 was generated by covalently linking rolipram to perillyl alcohol (POH) via a carbamate bond to form the rolipram-perillyl alcohol conjugate. We show here that NEO214 is effective against both temozolomide-sensitive and temozolomide-resistant glioma cells. Furthermore, NEO214 is effective for different mechanisms of temozolomide resistance: overexpression of MGMT (O 6 -methylguanine methyl-transferase); deficiency in specific mismatch repair proteins; and overexpression of base excision repair (BER) proteins. NEO214-induced cytotoxicity involves apoptosis triggered by endoplasmic retic-ulum (ER) stress, as well as activating the Death Receptor 5 (DR5)/TNF-related apoptosis-inducing ligand (TRAIL/ Apo2L) pathway. In vitro studies show that glioma cells treated with NEO214 express DR5 and exhibit cell death in the presence of recombinant TRAIL, a growth factor constitutively produced by astrocytes. Our in vitro 3D coculture data show that induction of DR5 in glioma cells with NEO214 and TRAIL cause tumor cell death very effectively and specifically for glioma cells. In vivo studies show that NEO214 has antitumor efficacy in orthotropic syngeneic rodent tumor models. Furthermore, NEO214 has therapeutic potential especially for brain tumors because this drug can cross the blood-brain barrier (BBB), and is effective in the TRAIL-rich astrocyte microenvironment. NEO214 is a strong candidate for use in the treatment of GBMs. Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis):

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Section: Cells and Reagentsmentioning

confidence: 99%

The Rolipram–Perillyl Alcohol Conjugate (NEO214) Is A Mediator of Cell Death through the Death Receptor Pathway

Cho

Thein

Swenson

et al. 2019

Molecular Cancer Therapeutics

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“…AuNPs have been used in this field, making it possible to destroy tumor cells noninvasively by RFA. [12][13][14] The optical properties of nanoshells can be utilized in tumorablation techniques with NIR light or RFA. Laroui et al developed nanoshells coated with gold, absorbing specific wavelengths of light.…”

Section: Gold Nmsmentioning

confidence: 99%

“…2 Many methods have been developed for tumor therapy, such as immunotherapy, 3,4 gene therapy, 5,6 and radiofrequency ablation (RFA). [7][8][9] Nevertheless, traditional radiotherapy, 10,11 surgery, [12][13][14] and especially chemotherapy 15,16 are still the major strategies utilized in clinical tumor treatments. However, chemotherapy has a number of problems, including nonspecific distribution of the drug and the lack of tumor-specific treatments.…”

Section: Introductionmentioning

confidence: 99%

Current applications and future prospects of nanomaterials in tumor therapy

Huang

Fan

Dong

et al. 2017

IJN

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Tumors are one of the most serious human diseases and cause numerous global deaths per year. In spite of many strategies applied in tumor therapy, such as radiation therapy, chemotherapy, surgery, and a combination of these treatments, tumors are still the foremost killer worldwide among human diseases, due to their specific limitations, such as multidrug resistance and side effects. Therefore, it is urgent and necessary to develop new strategies for tumor therapy. Recently, the fast development of nanoscience has paved the way for designing new strategies to treat tumors. Nanomaterials have shown great potential in tumor therapy, due to their unique properties, including passive targeting, hyperthermia effects, and tumor-specific inhibition. This review summarizes the recent progress using the innate antitumor properties of metallic and nonmetallic nanomaterials to treat tumors, and related challenges and prospects are discussed.

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“…TMZ together with perillyl alcohol formed a new complex NEO212 that was more cytotoxic than TMZ on the glioma cancer stem cells (GSCs) 17. NEO212 introduced into the culture medium containing GSCs induced 50% cell death after 72 hours of incubation, and interestingly, the dose of NEO212 was 7–40 fold lower than that of the TMZ.…”

Section: Introductionmentioning

confidence: 99%

“…NEO212 introduced into the culture medium containing GSCs induced 50% cell death after 72 hours of incubation, and interestingly, the dose of NEO212 was 7–40 fold lower than that of the TMZ. The sphere-forming assay performed on proneural GSCs indicated that NEO212 was 10-fold more potent than TMZ, and the induction of DNA damage in GSCs was independent of O 6 -methylguanine-DNA-methyltransferase (MGMT) 17. In another study, TMZ was conjugated with 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB), a non-specific chloride channel blocker 18.…”

Section: Introductionmentioning

confidence: 99%

Strategies of temozolomide in future glioblastoma treatment

Lee¹

2017

OTT

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Glioblastoma multiforme (GBM) may be one of the most challenging brain tumors to treat, as patients generally do not live more than 2 years. This review aimed to give a timely review of potential future treatments for GBM by looking at the latest strategies, involving mainly the use of temozolomide (TMZ). Although these studies were carried out either in vitro or in rodents, the findings collectively suggested that we are moving toward developing a more efficacious therapy for GBM patients. Nanoparticles preparation was, by far, the most extensively studied strategy for targeted brain delivery. Therefore, the first section of this review presents a treatment strategy using TMZ-loaded nanocarriers, which encompassed nanoparticles, nanoliposomes, and nanosponges. Besides nanocarriers, new complexes that were formed between TMZ and another chemical agent or molecule have shown increased cytotoxicity and antitumor activity. Another approach was by reducing GBM cell resistance to TMZ, and this was achieved either through the suppression of metabolic change occurring in the cells, inhibition of the DNA repair protein, or up-regulation of the protein that mediates autophagy. Finally, the review collates a list of substances that have demonstrated the ability to suppress tumor cell growth.

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A novel drug conjugate, NEO212, targeting proneural and mesenchymal subtypes of patient-derived glioma cancer stem cells

Cited by 25 publications

References 35 publications

The Rolipram–Perillyl Alcohol Conjugate (NEO214) Is A Mediator of Cell Death through the Death Receptor Pathway

The Rolipram–Perillyl Alcohol Conjugate (NEO214) Is A Mediator of Cell Death through the Death Receptor Pathway

Current applications and future prospects of nanomaterials in tumor therapy

Strategies of temozolomide in future glioblastoma treatment

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