Nicotine and Cancer: The Research
Nicotine itself is not classed as a carcinogen — the cancers of smoking are driven by the tar and nitrosamines in burnt tobacco — but nicotinic receptors are present on many tumour cells, and laboratory studies report effects on cell growth, migration and chemotherapy response in both directions. This page collects the published research on nicotine, its metabolites and cancer, 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 (25)
Newest first. Study types on this page — Review: 6 · Animal study: 2 · Cell study: 17. Each summary is written from the paper’s own abstract; follow the PubMed link for the full record.
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
Nicotine-induced CHRNA5 activation modulates CES1 expression, impacting head and neck squamous cell carcinoma recurrence and metastasis via MEK/ERK pathway
Cell study, 2024. Researchers studied head and neck cancer cells (including cell lines called Cal27, Fadu, HN6, and Tu686) in the lab, plus tumors grown in mice. Nicotine exposure increased the cancer cells' ability to grow, move, and invade by activating a nicotine receptor called CHRNA5, which in turn raised levels of another protein called CES1 through a cell signaling pathway called MEK/ERK. When the researchers reduced CHRNA5 in the cells, cancer cell growth, movement, and invasion decreased, but adding nicotine reversed that reduction.
Feng C, Mao W, Yuan C et al. (2024). Nicotine-induced CHRNA5 activation modulates CES1 expression, impacting head and neck squamous cell carcinoma recurrence and metastasis via MEK/ERK pathway. Cell Death Dis. — PubMed PMID: 39472448 · doi:10.1038/s41419-024-07178-4
Nicotine-mediated OTUD3 downregulation inhibits VEGF-C mRNA decay to promote lymphatic metastasis of human esophageal cancer
Cell study, 2021. This lab study looked at human esophageal cancer cells and tissue samples from heavy-smoking patients to understand how nicotine might help cancer spread to lymph nodes. The researchers found that nicotine lowers a protein called OTUD3, which sets off a chain of molecular events leading to higher levels of VEGF-C, a protein that promotes lymphatic spread of the cancer. Patients with heavy smoking history and low OTUD3 had worse outcomes, and the authors suggest OTUD3 could be a marker of prognosis or a target for future treatment.
Wang M, Li Y, Xiao Y et al. (2021). Nicotine-mediated OTUD3 downregulation inhibits VEGF-C mRNA decay to promote lymphatic metastasis of human esophageal cancer. Nat Commun. — PubMed PMID: 34853315 · doi:10.1038/s41467-021-27348-8
Low-Dose Nicotine Activates EGFR Signaling via α5-nAChR and Promotes Lung Adenocarcinoma Progression
Cell study, 2020. Researchers studied how low doses of nicotine, like those from secondhand smoke, affect lung adenocarcinoma, a type of lung cancer common in non-smokers. Lung cancer cell lines and tumor tissue from patients had high levels of a nicotine receptor called alpha5. In the cells, this receptor worked with a growth signal called EGFR, and low-dose nicotine needed the receptor to make the cancer cells grow, move and invade more. When the receptor was switched off, tumors grown in animals grew less, and patients whose tumors had more of the receptor had poorer survival. Most of these findings come from cells and animals, not from treating people.
Wang ML, Hsu YF, Liu CH et al. (2020). Low-Dose Nicotine Activates EGFR Signaling via α5-nAChR and Promotes Lung Adenocarcinoma Progression. Int J Mol Sci. — PubMed PMID: 32957649 · doi:10.3390/ijms21186829
Nicotine Promotes WRL68 Cells Proliferation Due to the Mutant p53 Gain-of-Function by Activating CDK6-p53-RS-PIN1-STAT1 Signaling Pathway
Cell study, 2020. Researchers exposed a line of human fetal liver cells, grown in the laboratory, to nicotine over a long period. Nicotine made the cells multiply faster, and the effect grew with higher doses and longer exposure. Nicotine also raised the level of a mutated form of p53, a protein that normally helps stop cells from growing out of control. Through a chain of other proteins, this mutated p53 drove cell growth. The authors suggest this could contribute to liver cancer in smokers, but the result comes only from cells in a dish.
Wang H, Chen L, Zhou T et al. (2020). Nicotine Promotes WRL68 Cells Proliferation Due to the Mutant p53 Gain-of-Function by Activating CDK6-p53-RS-PIN1-STAT1 Signaling Pathway. Chem Res Toxicol. — PubMed PMID: 32820905 · doi:10.1021/acs.chemrestox.0c00119
E-Cigarettes and Cancer Risk
Review, 2020. This review looks at how inhaling nicotine from e-cigarettes might be linked to cancer risk. The authors focus on nicotine's activation of the sympathetic nervous system, the body's 'fight or flight' stress system, and argue that this effect has been overlooked. Based on preclinical evidence, meaning laboratory and animal studies rather than studies in people, they report that this nervous-system activation by nicotine may help cancers start, grow and progress through several mechanisms. They note this may matter most for people with cancer, who may wrongly believe that e-cigarettes carry no risk compared with regular cigarettes.
Mravec B, Tibensky M, Horvathova L et al. (2020). E-Cigarettes and Cancer Risk. Cancer Prev Res (Phila). — PubMed PMID: 31619443 · doi:10.1158/1940-6207.CAPR-19-0346
Nicotine-induced resistance of non-small cell lung cancer to treatment--possible mechanisms
Review, 2016. This review looks at how nicotine might affect non-small cell lung cancer and how well its treatment works. The authors say nicotine is not a carcinogen, but lab and animal studies suggest it may help lung cancer cells resist chemotherapy and radiation. In those studies it also helped the cells grow, form new blood vessels, invade tissue and spread. The authors explain that these effects mainly work through nicotinic acetylcholine receptors on the cancer cells, which switch on growth signals and block the cell-death pathway.
Czyżykowski R, Połowinczak-Przybyłek J, Potemski P (2016). Nicotine-induced resistance of non-small cell lung cancer to treatment--possible mechanisms. Postepy Hig Med Dosw (Online). — PubMed PMID: 26943316 · doi:10.5604/17322693.1196391
Electronic cigarettes induce DNA strand breaks and cell death independently of nicotine in cell lines
Cell study, 2016. Researchers exposed normal skin-type cells and head and neck cancer cell lines in the lab to vapor extract from e-cigarettes, both with and without nicotine, for periods from 48 hours to 8 weeks. Cells exposed to the vapor survived and multiplied less, died more often, and had more breaks in their DNA. These effects appeared whether or not the vapor contained nicotine, which suggests that something in the vapor other than nicotine caused them. The results come only from cells grown in the lab, and the authors say the possible cancer-causing effects of e-cigarette vapor urgently need further study.
Yu V, Rahimy M, Korrapati A et al. (2016). Electronic cigarettes induce DNA strand breaks and cell death independently of nicotine in cell lines. Oral Oncol. — PubMed PMID: 26547127 · doi:10.1016/j.oraloncology.2015.10.018
Mechanisms of growth-promoting and tumor-protecting effects of epithelial nicotinic acetylcholine receptors
Cell study, 2015. This laboratory study looked at how nicotine may help cancer cells grow and survive, using human oral cancer cells and lung cancer cells grown in dishes. Nicotine switched on nicotinic receptors both on the cell surface and inside the mitochondria, the cell's power plants. The surface receptors teamed up with receptors for growth signals, and the mitochondrial receptors linked up with enzymes that block a pathway cells use to self-destruct; together this was tied to faster cell growth and more resistance to cell death caused by hydrogen peroxide. These results come from cells only, and the authors suggest these receptors could become a target for slowing or preventing cancer.
Chernyavsky AI, Shchepotin IB, Grando SA (2015). Mechanisms of growth-promoting and tumor-protecting effects of epithelial nicotinic acetylcholine receptors. Int Immunopharmacol. — PubMed PMID: 26071223 · doi:10.1016/j.intimp.2015.05.033
β-arrestin-1 mediates nicotine-induced metastasis through E2F1 target genes that modulate epithelial-mesenchymal transition
Cell study, 2015. Researchers studied how nicotine helps lung cancer cells (non-small cell lung cancer) change into a more mobile, invasive form that can spread, using several lung cancer cell lines. In these cells, nicotine switched on genes linked to spreading, and this depended on a helper protein called beta-arrestin-1 working with a gene-control protein called E2F1. Human lung tumor samples had more of these two proteins on the same genes. In mice given implanted human lung cancer cells, cells lacking beta-arrestin-1 formed smaller tumors and spread less; the nicotine findings themselves come from cell experiments.
Pillai S, Trevino J, Rawal B et al. (2015). β-arrestin-1 mediates nicotine-induced metastasis through E2F1 target genes that modulate epithelial-mesenchymal transition. Cancer Res. — PubMed PMID: 25600647 · doi:10.1158/0008-5472.CAN-14-0681
Connections of nicotine to cancer
Review, 2014. This opinion article reviews emerging evidence that nicotine itself may directly contribute to the start and growth of cancer. The authors list a growing number of cancers that have been reported to be connected to nicotine, including lung, head and neck, stomach, pancreas, gallbladder, liver, colon, breast, cervical, bladder and kidney cancers, and describe how nicotine may damage DNA, disrupt how cells use energy, and help abnormal cells grow and spread, partly by switching on nicotinic receptors. They also note that inherited differences in the genes for these receptors may affect how strongly a person is affected, and that these receptors might be targets for cancer treatment or prevention.
Grando SA (2014). Connections of nicotine to cancer. Nat Rev Cancer. — PubMed PMID: 24827506 · doi:10.1038/nrc3725
Intervention of nicotine on MNU-induced bladder cancer in rats
Animal study, 2011. Researchers gave rats bladder cancer with a chemical called MNU. Some of the rats were then fed nicotine at one of three doses (25, 15 or 5 mg/kg), three times a week for 8 weeks. By week 14, a mutant form of the p53 protein was found in 75.00%, 58.33% and 41.67% of the three nicotine groups, compared with 33.33% of rats that got MNU only, and higher doses and longer treatment went with higher rates. The authors concluded that nicotine may play a role in bladder cancer development, partly by raising mutant p53 levels; this result comes from rats only.
Liu D, Pan F, Li B et al. (2011). Intervention of nicotine on MNU-induced bladder cancer in rats. J Huazhong Univ Sci Technolog Med Sci. — PubMed PMID: 21336733 · doi:10.1007/s11596-011-0159-z
Habenular α5 nicotinic receptor subunit signalling controls nicotine intake
Animal study, 2011. This study in mice and rats looked at the α5 subunit, one part of the brain receptors that nicotine acts on. Mice born without the gene for this subunit took in much more nicotine. Their intake returned to normal when the subunit was put back into a small brain area called the medial habenula, and rats took in more nicotine when the subunit was reduced in that same area. The researchers concluded that nicotine switches on a pathway from the habenula to a connected area, the interpeduncular nucleus, and that this pathway sends a signal that limits how much nicotine the animals take, though these results come only from animals.
Fowler CD, Lu Q, Johnson PM et al. (2011). Habenular α5 nicotinic receptor subunit signalling controls nicotine intake. Nature. — PubMed PMID: 21278726 · doi:10.1038/nature09797
Nicotine induces DNA damage in human salivary glands
Cell study, 2009. Researchers took salivary gland (parotid) tissue from 10 patients having tumour surgery, using only the tumour-free part, separated it into single cells and exposed them in the laboratory to nicotine for 1 hour at 0.125 to 4.0 mM. Nicotine caused DNA damage that rose with the dose, ranging from 1.12-fold to 2.24-fold the level in unexposed cells. The lowest dose that caused significant damage, 0.25 mM, is only 10-fold higher than the highest nicotine levels reported in saliva after unrestricted smoking. This result comes only from cells in a dish; the authors say there is still no conclusive evidence that nicotine causes cancer, but that the safety of long-term nicotine replacement therapy should be carefully monitored.
Ginzkey C, Kampfinger K, Friehs G et al. (2009). Nicotine induces DNA damage in human salivary glands. Toxicol Lett. — PubMed PMID: 18852035 · doi:10.1016/j.toxlet.2008.09.009
Nicotine induces resistance to chemotherapy by modulating mitochondrial signaling in lung cancer
Cell study, 2009. Researchers exposed human lung cancer cells grown in the lab to nicotine (1 micromolar) and then to two chemotherapy drugs, cisplatin and etoposide, for 24 hours. Nicotine stopped the chemotherapy from triggering the cancer cells' normal self-destruct process (apoptosis) and helped the cells survive, working through survival signals (MAPK and Akt) and the cell's mitochondria. Blocking those signals, or using cells without working mitochondrial DNA, removed nicotine's protective effect. The authors say this could seriously weaken lung cancer treatment, but the result comes only from cells in a dish, not from patients.
Zhang J, Kamdar O, Le W et al. (2009). Nicotine induces resistance to chemotherapy by modulating mitochondrial signaling in lung cancer. Am J Respir Cell Mol Biol. — PubMed PMID: 18676776 · doi:10.1165/rcmb.2007-0277OC
Nicotine and apoptosis
Review, 2007. This review looks at how nicotine affects apoptosis, the process by which the body's cells are programmed to die when they are damaged or no longer needed. Nicotine acts on many kinds of cells beyond the nervous system, including immune cells, by attaching to nicotinic acetylcholine receptors. The authors say that through these receptors nicotine disrupts apoptosis, the growth of new blood vessels and cell-based immunity. Nicotine is not usually called a cancer-causing substance, but the authors note an ongoing debate over whether it helps tumors grow, and they argue that its effects on apoptosis are directly involved in diseases such as cancer and obstructive diseases.
Zeidler R, Albermann K, Lang S (2007). Nicotine and apoptosis. Apoptosis. — PubMed PMID: 17846896 · doi:10.1007/s10495-007-0102-8
Nicotine, lung and cancer
Review, 2007. This review looks at research on how nicotine acts on lung cancer and other cancers through nicotinic receptors. These receptors are found on normal airway cells and on lung cancer and mesothelioma cells. The studies it covers report that nicotine can make several kinds of cancer cells grow, including colon, stomach and lung cancer cells. They also report that nicotine triggers growth signals, helps tumors grow in living animals, and can protect lung cancer cells from being killed by chemotherapy drugs. The authors conclude that nicotine may give early tumors a growth and survival advantage, but they found no evidence that nicotine itself causes cancer.
Grozio A, Catassi A, Cavalieri Z et al. (2007). Nicotine, lung and cancer. Anticancer Agents Med Chem. — PubMed PMID: 17630920 · doi:10.2174/187152007781058587
Nicotine inhibits apoptosis induced by cisplatin in human oral cancer cells
Cell study, 2007. Researchers tested nicotine on a line of human oral (mouth) cancer cells grown in the lab, alone and together with cisplatin, a chemotherapy drug commonly used for advanced oral cancer. Nicotine reduced the cancer-cell death that cisplatin normally causes. It did this by switching on the Akt pathway and raising survivin, a protein that keeps cells alive; blocking survivin or the Akt pathway took away much of nicotine's protective effect. These results come only from cells in a dish, and the authors suggest nicotine exposure might weaken how well chemotherapy kills cancer cells.
Xu J, Huang H, Pan C et al. (2007). Nicotine inhibits apoptosis induced by cisplatin in human oral cancer cells. Int J Oral Maxillofac Surg. — PubMed PMID: 17611077 · doi:10.1016/j.ijom.2007.05.016
Nicotine stimulates human lung cancer cell growth by inducing fibronectin expression
Cell study, 2007. Researchers studied non-small cell lung cancer cells grown in the lab and found that nicotine made them multiply faster, especially by 5 days, though it did not change how many cells died off. Nicotine triggered the cells to make more of a protein called fibronectin by acting on a nicotinic receptor (alpha7 nAChR) and activating two cell-signaling pathways (ERK and PI3-K/mTOR); blocking fibronectin's receptor or those signaling pathways stopped nicotine from speeding up cell growth. The paper suggests fibronectin and its receptor could be targets for anti-lung-cancer treatments.
Zheng Y, Ritzenthaler JD, Roman J et al. (2007). Nicotine stimulates human lung cancer cell growth by inducing fibronectin expression. Am J Respir Cell Mol Biol. — PubMed PMID: 17600315 · doi:10.1165/rcmb.2007-0051OC
Nicotine-mediated cell proliferation and angiogenesis: new twists to an old story
Review, 2006. This review looks at how nicotine acts on the body's nicotinic acetylcholine receptors. These receptors are found in the brain and at nerve-muscle junctions, and also in other tissues such as the lung. The authors say nicotine does not cause cancer by itself. However, they describe research showing that when nicotine activates these receptors outside the brain, it can make cells multiply and help new blood vessels grow, and they explain the cell signals involved. They suggest that the steps in this pathway could become targets for new anti-cancer treatments.
Dasgupta P, Chellappan SP (2006). Nicotine-mediated cell proliferation and angiogenesis: new twists to an old story. Cell Cycle. — PubMed PMID: 17102610 · doi:10.4161/cc.5.20.3366
Nicotine inhibits apoptosis induced by chemotherapeutic drugs by up-regulating XIAP and survivin
Cell study, 2006. Researchers tested whether nicotine changes how well three chemotherapy drugs (gemcitabine, cisplatin and taxol) kill human non-small cell lung cancer cells grown in the lab. Nicotine protected the cancer cells from being killed by these drugs, and it did so by raising two survival proteins in the cells, XIAP and survivin. When those proteins were removed, the protective effect went away. The effect ran through a type of nicotinic receptor and the Akt signaling pathway. This was only shown in cells, and the authors suggest nicotine exposure might weaken how well chemotherapy works.
Dasgupta P, Kinkade R, Joshi B et al. (2006). Nicotine inhibits apoptosis induced by chemotherapeutic drugs by up-regulating XIAP and survivin. Proc Natl Acad Sci U S A. — PubMed PMID: 16601104 · doi:10.1073/pnas.0509313103
Carcinogenic effect of nicotine on normal mammary ductal epithelial cells and the protective role of beta-carotene
Cell study, 2003. Researchers exposed normal breast duct lining cells to nicotine in the laboratory to see whether nicotine acts on them directly. Nicotine significantly increased how fast the cells multiplied and how much estrogen receptor they made, and it also raised colony formation; the effect was stronger at the lower concentration tested (650 micrograms per millilitre), while a higher dose damaged the cells. Adding beta-carotene, an antioxidant, significantly reduced the faster multiplication caused by the lower nicotine dose and prevented the cell damage from the higher dose, but it did not significantly change the rise in estrogen receptor, although that showed a downward trend. These results come only from cells grown in the laboratory, not from people or animals.
Mazhari NJ, Mandal AK, Thusoo TK (2003). Carcinogenic effect of nicotine on normal mammary ductal epithelial cells and the protective role of beta-carotene. Indian J Pathol Microbiol. — PubMed PMID: 15027713
Induction of DNA fragmentation by nicotine in human myelogenous leukemic cell lines
Cell study, 1998. Researchers tested nicotine on human leukemia cell lines (HL-60 and ML-1) grown in the lab. High doses of nicotine did not cause these cells to mature into normal blood cell types, but nicotine did cause DNA fragmentation (a sign of cell death) in the leukemia cells, while normal human blood cells were not affected the same way. Nicotine also raised calcium levels inside the leukemia cells more than in normal cells, and the researchers suggest this calcium rise is needed to trigger the DNA breakdown.
Yoshida H, Sakagami H, Yamanaka Y et al. (1998). Induction of DNA fragmentation by nicotine in human myelogenous leukemic cell lines. Anticancer Res. — PubMed PMID: 9703901
Growth factor-mediated mechanisms of nicotine-dependent carcinogenesis
Cell study, 1994. Researchers studied cervical cancer cells in a lab dish to see how nicotine affects two signaling proteins, TNF alpha and TGF beta, that cells take in and normally break down quickly. At low concentrations (0.05-0.25%) nicotine slowed cell growth, and above 0.5% it caused strong cell death. At a middle concentration (0.1%), nicotine prevented these two proteins from being broken down inside the cell for up to 5 days, instead of the normal one day, and caused TGF beta to build up in the cell's nucleus, where it increased RNA production and shifted its effect from promoting growth to strongly inhibiting it. The cell-surface receptors for these proteins did not change. The authors discuss blocking this protein breakdown as one possible way nicotine or tobacco exposure could contribute to cancer development.
Rakowicz-Szulczynska EM, McIntosh DG, Smith M (1994). Growth factor-mediated mechanisms of nicotine-dependent carcinogenesis. Carcinogenesis. — PubMed PMID: 7923576 · doi:10.1093/carcin/15.9.1839
Nicotine inhibition of apoptosis suggests a role in tumor promotion
Cell study, 1993. Researchers tested in laboratory cell cultures whether nicotine affects apoptosis, the built-in self-destruct process that helps the body get rid of damaged cells before they can turn into tumors. Nicotine blocked apoptosis triggered by several different stresses, including an immune signaling protein, UV light, chemotherapy drugs and a calcium-raising chemical. This happened in normal and cancer-like cells from several species and tissues, including tumor cell types linked to tobacco use. Cotinine, nicotine's main breakdown product, also blocked apoptosis, but a cancer-causing chemical found in tobacco did not. The authors suggest this effect could contribute to tobacco-related cancers and make cancer treatments work less well. The findings come from cells only, not from animals or people.
Wright SC, Zhong J, Zheng H et al. (1993). Nicotine inhibition of apoptosis suggests a role in tumor promotion. FASEB J. — PubMed PMID: 8370474
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Connections
- The Cell Cycle & How Cancer Hijacks It — interactive animation
- Nicotine: The Research
- The Nicotine Patch, animated
- Nicotinic Acetylcholine Receptors
- Cigarette Smoke — what burnt tobacco adds that nicotine alone does not
- Brain and Memory
- Mood and Mental Health
- Inflammation and Immunity
- Heart and Blood Vessels
- Metabolism and Weight
- Addiction and Withdrawal
- Patches, Gum and Delivery
- Toxicity and Safety