Nicotine, Glioblastoma and Brain Tumours: The Research
Glioblastoma and other glioma cells carry nicotinic receptors, and laboratory studies have tested how nicotine and its metabolites affect their growth, invasion and response to chemotherapy. This page collects the published research on nicotine and brain tumours, each paper summarised in plain language with its PubMed record.
This collection is research only: papers found on PubMed, each described as its own abstract reports it. Cell and animal results are labelled as such, and harms are listed beside benefits. It is not medical advice.
Table of Contents
Research at a Glance
What kind of study each paper on this page is, and when the papers were published. Hover over a bar for its count.
The Papers (21)
Newest first. Study types on this page — Human observational study: 1 · Review: 2 · Animal study: 3 · Cell study: 14 · Other: 1. Each summary is written from the paper’s own abstract; follow the PubMed link for the full record.
Nicotinic Acetylcholine Receptor of α7 Subtype is Linked to Glioblastoma Cholinergic Heterogeneity
Cell study, 2026. Researchers studied glioblastoma cells in the lab (the U87MG cell line) to see how a specific receptor that nicotine normally acts on, called the alpha-7 nicotinic acetylcholine receptor, might contribute to how diverse and complex these brain tumors become. Using chemicals that turn this receptor on or off, they found it changed the activity of several related receptor genes, and blocking it with a toxin increased how many tumor cells survived. The study also found changes in several proteins involved in cell structure and metabolism, suggesting this receptor may be one of several factors shaping tumor diversity, but the authors note this was done in only one cell line and needs further testing in other models before drawing broader conclusions.
Gondarenko E, Mazur D, Siniavin A et al. (2026). Nicotinic Acetylcholine Receptor of α7 Subtype is Linked to Glioblastoma Cholinergic Heterogeneity. J Mol Neurosci. — PubMed PMID: 42012794 · doi:10.1007/s12031-026-02523-y
Investigating the potential risk of nicotine exposure on glioblastoma: Integrating Mendelian randomization and network toxicology analysis
Other, 2026. This study used only computer and database analyses to ask whether nicotine exposure might be linked to glioblastoma, an aggressive brain cancer. It used a genetic method called Mendelian randomization to look at genetically predicted blood levels of cotinine, which the body makes from nicotine, and reported a causal link between cotinine and glioblastoma. Database searches found 194 genes that nicotine might affect, involved in viral infection, immunity, cancer and metabolism, and narrowed these to six core genes, including NFκB1, HIF1α and MMP2. No patients, animals or cells were tested directly, and the authors present the results as new leads for future research on nicotine-related exposure and glioblastoma risk.
Yu S, Long M, Huang N et al. (2026). Investigating the potential risk of nicotine exposure on glioblastoma: Integrating Mendelian randomization and network toxicology analysis. Comput Biol Chem. — PubMed PMID: 41967427 · doi:10.1016/j.compbiolchem.2026.109061
The dopamine paradox in glioblastoma oncology: methylxanthine therapy against nicotine-driven pathogenesis
Review, 2025. This editorial discusses how brain tumor cells (glioblastoma) use dopamine-related signaling to grow, describing two opposing pathways. It explains that nicotine, by acting on nicotinic receptors, may worsen glioblastoma progression by activating one of these pro-tumor pathways, while caffeine and theophylline were proposed as potential counteracting agents through the opposite pathway. The piece is a theoretical discussion calling for more research rather than new experimental data.
Mursaleen M, Tahir M, Suleman MU et al. (2025). The dopamine paradox in glioblastoma oncology: methylxanthine therapy against nicotine-driven pathogenesis. Ann Med Surg (Lond). — PubMed PMID: 41180641 · doi:10.1097/MS9.0000000000003853
The Distinct Biological Effects of 6-Hydroxy-L-Nicotine in Representative Cancer Cell Lines
Cell study, 2024. Researchers tested 6-hydroxy-L-nicotine, a compound made from nicotine, on three kinds of cancer cells grown in the lab (lung, breast and brain-tumour cells) and on two kinds of normal lung and breast cells. Computer modelling suggested the compound may bind to nicotinic receptors, the same receptor family nicotine acts on. In the lab dishes it made the brain-tumour (glioblastoma) cells grow more, held back the breast cancer cells, and had no effect on the lung cancer cells. The normal cells stayed alive at the same rate, but all of these results come from cells in dishes and computer models, not from animals or people.
Postu PA, Boiangiu RS, Mihasan M et al. (2024). The Distinct Biological Effects of 6-Hydroxy-L-Nicotine in Representative Cancer Cell Lines. Molecules. — PubMed PMID: 39683752 · doi:10.3390/molecules29235593
Terahertz label-free detection of nicotine-induced neural cell changes and the underlying mechanisms
Cell study, 2023. Researchers used a terahertz light-based scanning method to study how nicotine affects two types of brain cells grown in the lab: normal brain cells and brain tumor cells. In normal brain cells, low-dose nicotine produced a smaller signal change and high-dose nicotine a larger one compared to untreated cells, while in the brain tumor cells nicotine always produced a smaller signal than untreated cells. The signal changes matched changes in cell number, composition, and shape, letting the method tell cell health and type apart without stains or damage to the cells.
Tang M, Zhang M, Fu Y et al. (2023). Terahertz label-free detection of nicotine-induced neural cell changes and the underlying mechanisms. Biosens Bioelectron. — PubMed PMID: 37751650 · doi:10.1016/j.bios.2023.115697
Under lithium carbonate administration, nicotine triggers cell dysfunction in human glioblastoma U-251MG cells, which is distinct from cotinine
Cell study, 2022. This lab study tested nicotine and its breakdown product cotinine, alone and combined with the mood-stabilizer drug lithium carbonate, on human glioblastoma brain tumor cells grown in a dish. Nicotine slowed the growth of these cancer cells, and adding lithium carbonate slowed growth even further, along with signs of cell damage (mitotic catastrophe) and a rise in reactive oxygen molecules called superoxide anion radicals; cotinine did not produce these effects. Blocking nicotinic receptors with a drug called mecamylamine reversed nicotine's growth-slowing effect, showing it worked through those receptors. The researchers frame the findings as insight into risks of smoking while taking lithium carbonate, not as a treatment finding.
Kato S (2022). Under lithium carbonate administration, nicotine triggers cell dysfunction in human glioblastoma U-251MG cells, which is distinct from cotinine. Med Int (Lond). — PubMed PMID: 36698501 · doi:10.3892/mi.2022.44
Evidence of a dual mechanism of action underlying the anti-proliferative and cytotoxic effects of ammonium-alkyloxy-stilbene-based α7- and α9-nicotinic ligands on glioblastoma cells
Cell study, 2022. Researchers tested two new lab compounds, designed from a nicotine-receptor-binding molecule, against glioblastoma brain tumor cells grown in dishes (U87MG cells) and compared effects to mouse brain support cells. Both compounds reduced tumor cell survival and energy production more than the original nicotine-receptor compound, while being gentler on normal mouse astrocytes; one of them also caused more cell-cycle arrest and cell death. When the cells' nicotinic receptor (alpha9) was reduced, the compounds worked less well, but blocking the same receptor with a different blocker did not change some of the effects, suggesting the compounds act partly through nicotinic receptors and partly through other, non-nicotinic pathways.
Pucci S, Bolchi C, Bavo F et al. (2022). Evidence of a dual mechanism of action underlying the anti-proliferative and cytotoxic effects of ammonium-alkyloxy-stilbene-based α7- and α9-nicotinic ligands on glioblastoma cells. Pharmacol Res. — PubMed PMID: 34756924 · doi:10.1016/j.phrs.2021.105959
Antiproliferative effect of GTS-21 in glioblastoma cells
Cell study, 2021. Researchers tested glioblastoma brain tumour cells (from cell lines and from patient tumour samples) for genes related to the body's acetylcholine signaling system. They then treated the cancer cells with GTS-21, a compound that activates one type of nicotinic receptor (alpha 7), as well as with acetylcholine or nicotine, and measured cell growth over 24, 48 and 72 hours. GTS-21 slowed the growth of the glioblastoma cells in a dose- and time-dependent way, and blocking that same receptor with another compound restored growth in some but not all of the cell lines tested. The authors say this suggests the approach deserves further study as a possible treatment strategy, but all results were in lab-grown cells, not in animals or people.
Kolodziej MA, Gött H, Kopischke B et al. (2021). Antiproliferative effect of GTS-21 in glioblastoma cells. Oncol Lett. — PubMed PMID: 34539863 · doi:10.3892/ol.2021.13020
α-Conotoxins and α-Cobratoxin Promote, while Lipoxygenase and Cyclooxygenase Inhibitors Suppress the Proliferation of Glioma C6 Cells
Cell study, 2021. Researchers tested how different substances affected the growth of rat C6 glioma (brain tumor) cells in the lab. Two snake/snail-derived toxins that block nicotinic receptors actually increased the cancer cells' growth, while nicotine itself had almost no effect at the concentrations tested. Separately, two lipoxygenase-inhibiting compounds slowed and killed the cancer cells, and blocking nicotinic receptors partly weakened that effect after 24 hours but not later. The cells were also shown to carry several types of nicotinic receptor subunits, which the authors say is the first evidence that these receptors play a role in this type of brain tumor cell growth.
Terpinskaya TI, Osipov AV, Kryukova EV et al. (2021). α-Conotoxins and α-Cobratoxin Promote, while Lipoxygenase and Cyclooxygenase Inhibitors Suppress the Proliferation of Glioma C6 Cells. Mar Drugs. — PubMed PMID: 33669933 · doi:10.3390/md19020118
Choline and nicotine increase glioblastoma cell proliferation by binding and activating α7- and α9- containing nicotinic receptors
Cell study, 2021. Researchers tested whether nicotine and choline affect glioblastoma, the most common and most aggressive type of brain tumour that starts in the brain. They used two lines of human glioblastoma cells grown in the lab, one of them resistant to the chemotherapy drug temozolomide. Both nicotine and choline made the tumour cells multiply faster and switched on cell pathways that help cells grow and avoid dying. These effects went away when the alpha-7 or alpha-9 nicotinic receptors were blocked or switched off. Because these results come only from cells in a dish, the authors suggest these receptors might play a part in how aggressive the tumour is and could become targets for new treatments.
Pucci S, Fasoli F, Moretti M et al. (2021). Choline and nicotine increase glioblastoma cell proliferation by binding and activating α7- and α9- containing nicotinic receptors. Pharmacol Res. — PubMed PMID: 33276105 · doi:10.1016/j.phrs.2020.105336
Nicotine promotes brain metastasis by polarizing microglia and suppressing innate immune function
Animal study, 2020. Researchers looked at 281 lung cancer patients whose cancer had spread, and found that smokers had a much higher rate of the cancer spreading to the brain. In mice, nicotine increased the spread of lung cancer to the brain by shifting the brain's immune cells (microglia) into a state that releases growth signals helping tumors grow and weakens those cells' ability to engulf and clear cancer cells. Removing the microglia blocked this effect, and a plant compound called parthenolide reduced the spread to the brain by blocking this shift. The authors say the results point to a possible risk of using nicotine to help people quit smoking.
Wu SY, Xing F, Sharma S et al. (2020). Nicotine promotes brain metastasis by polarizing microglia and suppressing innate immune function. J Exp Med. — PubMed PMID: 32496556 · doi:10.1084/jem.20191131
Potential effects of nicotine on glioblastoma and chemoradiotherapy: a review
Review, 2019. This review looked at how nicotine might affect glioblastoma, an aggressive brain cancer, and its treatment with radiation and chemotherapy. The authors note that about 16-28% of people with glioblastoma keep smoking after diagnosis and during treatment, and that published research on how smoking and nicotine affect glioblastoma care is sparse. Drawing on cell and tumor research, including studies of other cancers, they describe cell pathways that nicotine may act on to help the tumor grow and resist chemotherapy drugs. They conclude that understanding these effects should let doctors give patients with glioblastoma evidence-based advice about continuing to use nicotine-containing products during treatment.
McConnell DD, Carr SB, Litofsky NS (2019). Potential effects of nicotine on glioblastoma and chemoradiotherapy: a review. Expert Rev Neurother. — PubMed PMID: 31092064 · doi:10.1080/14737175.2019.1617701
Liposome-Based Systemic Glioma-Targeted Drug Delivery Enabled by All-d Peptides
Animal study, 2016. Researchers built a drug-carrying liposome coated with two peptide targeting molecules, one of which binds nicotinic acetylcholine receptors to help the particle cross the blood-brain barrier, and a second that homes to brain tumor blood vessels and tumor cells. In mice with brain tumors, this double-targeted liposome entered tumor cells and blood vessel cells more effectively than plain liposomes or single-peptide versions, and when loaded with a chemotherapy drug it produced the strongest anti-tumor, anti-blood-vessel-growth effects among all versions tested.
Ying M, Zhan C, Wang S et al. (2016). Liposome-Based Systemic Glioma-Targeted Drug Delivery Enabled by All-d Peptides. ACS Appl Mater Interfaces. — PubMed PMID: 27797175 · doi:10.1021/acsami.6b10146
Liposome-based glioma targeted drug delivery enabled by stable peptide ligands
Animal study, 2015. Researchers designed tiny fat-based particles (liposomes) coated with two targeting molecules to deliver the chemotherapy drug doxorubicin across the blood-brain barrier to glioma brain tumors. One of the targeting molecules binds to nicotinic acetylcholine receptors found on the blood-brain barrier, helping the particles cross into the brain, while the second molecule targets the tumor itself. In mice with glioma, these dual-targeted particles crossed the barrier more effectively in lab and imaging tests, and mice treated with them lived longer on average than those given untargeted particles or particles with only one targeting molecule.
Wei X, Gao J, Zhan C et al. (2015). Liposome-based glioma targeted drug delivery enabled by stable peptide ligands. J Control Release. — PubMed PMID: 26428462 · doi:10.1016/j.jconrel.2015.09.059
A D-peptide ligand of nicotine acetylcholine receptors for brain-targeted drug delivery
Cell study, 2015. Researchers designed a lab-made mirror-image peptide that binds to nicotine receptors (the same receptors nicotine acts on) to help ferry drugs across the blood-brain barrier. In cell-based blood-brain-barrier models, this engineered peptide was more stable and crossed the barrier more efficiently than the normal version, and when attached to drug-carrying particles in these cell models it improved delivery of a chemotherapy drug used against glioblastoma brain tumors. This is lab/cell-level work, not a test in animals or people.
Wei X, Zhan C, Shen Q et al. (2015). A D-peptide ligand of nicotine acetylcholine receptors for brain-targeted drug delivery. Angew Chem Int Ed Engl. — PubMed PMID: 25600241 · doi:10.1002/anie.201411226
Nicotine enhances proliferation, migration, and radioresistance of human malignant glioma cells through EGFR activation
Cell study, 2013. Researchers tested nicotine on two lines of human brain tumor (malignant glioma) cells grown in the lab. At levels similar to those found in long-term smokers, nicotine made the tumor cells grow, move and form colonies more, and made them more resistant to radiation treatment. Nicotine switched on a growth-signaling receptor called EGFR and the AKT and ERK pathways downstream of it, and drugs that block these pathways reduced the effects. These results come only from cells in a dish, not from animals or people.
Khalil AA, Jameson MJ, Broaddus WC et al. (2013). Nicotine enhances proliferation, migration, and radioresistance of human malignant glioma cells through EGFR activation. Brain Tumor Pathol. — PubMed PMID: 22614999 · doi:10.1007/s10014-012-0101-5
Characterization of a multiple ligand-gated ion channel cellular membrane affinity chromatography column and identification of endogenously expressed receptors in astrocytoma cell lines
Cell study, 2008. Researchers built lab chromatography columns coated with membranes from two human brain tumor (astrocytoma) cell lines and used them to test which receptors were present. Using a radioactive tracer and nicotine itself as one of the test chemicals, they showed that these tumor cell membranes carry two types of nicotinic acetylcholine receptors (the receptors nicotine acts on), along with GABA and NMDA receptors. The study's purpose was to demonstrate this column method as a tool for studying receptor binding, not to test any treatment or outcome in people or animals.
Kitabatake T, Moaddel R, Cole R et al. (2008). Characterization of a multiple ligand-gated ion channel cellular membrane affinity chromatography column and identification of endogenously expressed receptors in astrocytoma cell lines. Anal Chem. — PubMed PMID: 18847217 · doi:10.1021/ac8016407
Hypothalamic digoxin mediated model for oncogenesis
Human observational study, 2001. This study measured blood markers in patients with brain tumors (glioblastoma and a type of lymphoma), looking at a cascade of metabolic and hormone-pathway changes linked to a substance called digoxin. Among many markers measured, blood nicotine levels were reported as elevated in these cancer patients, alongside several other substances, as part of a broader proposed mechanism for how the tumors might develop.
Kurup RK, Nair R, Kurup PA (2001). Hypothalamic digoxin mediated model for oncogenesis. J Exp Clin Cancer Res. — PubMed PMID: 11876554
Expression of TRH and TRH-like peptides in a human glioblastoma-astrocytoma cell line (U-373-MG)
Cell study, 2000. Researchers studied a human glioblastoma-astrocytoma cell line and found it produces and releases TRH and TRH-related peptides, with genetic evidence confirming the cells make the TRH precursor. When the cells were treated with nicotine (which activates nicotinic receptors), production of TRH and these related compounds decreased, while a different compound that activates muscarinic receptors increased it.
García SI, Porto PI, Martinez VN et al. (2000). Expression of TRH and TRH-like peptides in a human glioblastoma-astrocytoma cell line (U-373-MG). J Endocrinol. — PubMed PMID: 10974663 · doi:10.1677/joe.0.1660697
Calcium mobilization during nicotine-induced cell death in human glioma and glioblastoma cell lines
Cell study, 1998. Researchers exposed three human brain tumor cell lines (one glioma and two glioblastoma lines) to nicotine in the laboratory. Nicotine killed the tumor cells, and higher doses killed more of them. It did not break up their DNA in the pattern seen when leukemia cells die by programmed cell death. Nicotine quickly raised calcium levels inside the cells, more in the nucleus than in the rest of the cell, and the authors suggest this build-up of calcium in the nucleus is an important early step in nicotine-induced cell death. These results come only from cells grown in the lab, not from people or animals.
Yamamura M, Amano Y, Sakagami H et al. (1998). Calcium mobilization during nicotine-induced cell death in human glioma and glioblastoma cell lines. Anticancer Res. — PubMed PMID: 9703899
Effects of neurotransmitters on calcium efflux from cultured glioma cells
Cell study, 1981. Researchers studied cultured human glioma (brain tumor) cells to see what controls calcium release from the cells. They tested several neurotransmitters and found that glutamate, glycine, stimulation of beta-adrenergic receptors, and stimulation of cholinergic receptors with a nicotine-like drug called carbachol all increased calcium release, while GABA and alpha-adrenergic stimulation did not. The carbachol effect was blocked by atropine and by hexamethonium, both receptor-blocking drugs, and cyclic AMP and cyclic GMP also increased calcium release. The study breaks the calcium release into four separate pools inside the cell and discusses how this calcium signaling might work in communication between brain support cells (glia) and nerve cells.
Lazarewicz JW, Kanje M (1981). Effects of neurotransmitters on calcium efflux from cultured glioma cells. J Neurosci Res. — PubMed PMID: 6117661 · doi:10.1002/jnr.490060303
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Connections
- The Cell Cycle & How Cancer Hijacks It — interactive animation
- Nicotine: The Research
- Dr. Bryan Ardis on this subject — his claims, presented on their own pages and kept separate from this research collection
- The Nicotine Patch, animated
- Nicotinic Acetylcholine Receptors
- Cigarette Smoke — what burnt tobacco adds that nicotine alone does not
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