ArticleInvestigational new drugs2014
Oxidative cytotoxic agent withaferin A resensitizes temozolomide-resistant glioblastomas via MGMT depletion and induces apoptosis through Akt/mTOR pathway inhibitory modulation.
Article in Investigational new drugs, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 76 citations in OpenAlex.
- Article
- A Comprehensive Analysis of Natural Bioactive Molecules for the Treatment and Control of Glioblastoma Multiforme (GBM) Targeting Underlying Molecular Mechanism.Chemistry & biodiversity · 2026Review
- Review
- Small molecular weight polyfluoroalkyl phosphonates induce ROS-mediated cytotoxicity in glioblastoma cells: a molecular mechanism study.Scientific reports · 2025Article
- Overview of Ayurveda and Ashwagandha: Bioactive Phytochemicals and Potential Applications to Gliomas.Molecules (Basel, Switzerland) · 2025Review
- Role of Non-coding RNAs in the Response of Glioblastoma to Temozolomide.Molecular neurobiology · 2025Review
- Phyto-therapeutics as anti-cancer agents in breast cancer: Pathway targeting and mechanistic elucidation.Saudi journal of biological sciences · 2024Review
- SoloxoloneFrontiers in pharmacology · 2024Article
- An Insight into Emerging Phytocompounds for Glioblastoma Multiforme Therapy.Cardiovascular & hematological agents in medicinal chemistry · 2024Review
- Withaferin A: A Dietary Supplement with Promising Potential as an Anti-Tumor Therapeutic for Cancer Treatment - Pharmacology and Mechanisms.Drug design, development and therapy · 2023Review
- Characterization of EGFR-reprogrammable temozolomide-resistant cells in a model of glioblastoma.Cell death discovery · 2022Article
- Review
- Perspectives on natural compounds in chemoprevention and treatment of cancer: an update with new promising compounds.European journal of cancer (Oxford, England : 1990) · 2021Review
- Integrative Analysis of a Novel Eleven-Small Nucleolar RNA Prognostic Signature in Patients With Lower Grade Glioma.Frontiers in oncology · 2021Article
- Overexpression miR-486-3p Promoted by Allicin Enhances Temozolomide Sensitivity in Glioblastoma Via Targeting MGMT.Neuromolecular medicine · 2020Article
- Matteucinol, isolated from Miconia chamissois, induces apoptosis in human glioblastoma lines via the intrinsic pathway and inhibits angiogenesis and tumor growth in vivo.Investigational new drugs · 2020Article
- Molecular Targets for Combined Therapeutic Strategies to Limit Glioblastoma Cell Migration and Invasion.Frontiers in pharmacology · 2020Article
- Current promising treatment strategy for glioblastoma multiform: A review.Oncology reviews · 2019Article
- Modulatory effects of Amukkara Choornam on Candida albicans biofilm: in vitro and in vivo study.Molecular biology reports · 2019Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 4 institutions in 1 country.
Funding
Abstract
Temozolomide (TMZ) has remained the chemotherapy of choice in patients with glioblastoma multiforme (GBM) primarily due to the lack of more effective drugs. Tumors, however, quickly develop resistance to this line of treatment creating a critical need for alternative approaches and strategies to resensitize the cells. Withaferin A (WA), a steroidal lactone derived from several genera of the Solanaceae plant family has previously demonstrated potent anti-cancer activity in multiple tumor models. Here, we examine the effects of WA against TMZ-resistant GBM cells as a monotherapy and in combination with TMZ. WA prevented GBM cell proliferation by dose-dependent G2/M cell cycle arrest and cell death through both intrinsic and extrinsic apoptotic pathways. This effect correlated with depletion of principle proteins of the Akt/mTOR and MAPK survival and proliferation pathways with diminished phosphorylation of Akt, mTOR, and p70 S6K but compensatory activation of ERK1/2. Depletion of tyrosine kinase cell surface receptors c-Met, EGFR, and Her2 was also observed. WA demonstrated induction of N-acetyl-L-cysteine-repressible oxidative stress as measured directly and through a subsequent heat shock response with HSP32 and HSP70 upregulation and decreased HSF1. Finally, pretreatment of TMZ-resistant GBM cells with WA was associated with O6-methylguanine-DNA methyltransferase (MGMT) depletion which potentiated TMZ-mediated MGMT degradation. Combination treatment with both WA and TMZ resulted in resensitization of MGMT-mediated TMZ-resistance but not resistance through mismatch repair mutations. These studies suggest great clinical potential for the utilization of WA in TMZ-resistant GBM as both a monotherapy and a resensitizer in combination with the standard chemotherapeutic agent TMZ.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.