The Influence of Nicotine on Lung Tumor Growth, Cancer Chemotherapy, and Chemotherapy-Induced Peripheral Neuropathy

Abstract

Studies in animal models have suggested that nicotine, an agonist of nicotinic acetylcholine receptors, may have the potential to prevent and/or reverse the peripheral neuropathy induced by cancer chemotherapeutic drugs, such as paclitaxel and oxaliplatin. However, a large body of evidence suggests that nicotine may also stimulate lung tumor growth and/or interfere with the effectiveness of cancer chemotherapy. Whereas the reported proliferative effects of nicotine are highly variable, the antagonism of antitumor drug efficacy is more consistent, although this latter effect has been demonstrated primarily in cell culture studies. In contrast, in vitro and in vivo studies from our own laboratory indicate that nicotine fails to enhance the growth of nonsmall cell lung cancer cells or attenuate the effects of chemotherapy (paclitaxel). Given the inconsistencies in the literature, coupled with our own findings, the weight of evidence suggests that caution may be warranted in proposing to use nicotine to mitigate chemotherapy-induced peripheral neuropathy in cancer patients receiving chemotherapy. Conversely, clinical trials could be performed in patients who have completed therapy and are considered to be disease-free to determine whether nicotine, in the form of commercially available patches or gum, is effective in alleviating peripheral neuropathy symptoms.

Cancer potencies and margin of exposure used for comparative risk assessment of heated tobacco products and electronic cigarettes aerosols with cigarette smoke

“…While a few studies reported cardiovascular effects related to nicotine exposure, like increase of systolic and diastolic blood pressures as well as heart rate, thrombosis, inflammatory effects or atherosclerosis (Heeschen et al 2001 ; Benowitz et al 2002 ; Lee and Cooke 2011 ; Benowitz and Burbank 2016 ; Moheimani et al 2017 ; Franzen et al 2018 ), other concluded the absence of nicotine effect on cardiovascular system (Joseph et al 1996 ; Zevin et al 1998 ; Farsalinos et al 2016 ; D’Ruiz et al 2017 ). Whereas some studies described potential role played by nicotine in the development of lung cancer, as tumor promoter, proliferative agent, or interfering with cancer chemotherapy (Minna 2003 ; Grozio et al 2007 ; Catassi et al 2008 ; Guo et al 2011 ; Kyte and Gewirtz 2018 ), other studies indicated that nicotine has the potential to prevent them (Kunze et al 1999 ) or at least does not contribute to their occurrence (Murray et al 2009 ). In vitro (Bavarva et al 2013 ; Momi et al, 2013 ) and in vivo transgenic rodent models have been established to prove the role of nicotine in cancer progression pathways, which has however not been demonstrated in human cancer (Haussmann and Fariss 2016 ).…”

Recent Developments of Novel Pharmacologic Therapeutics for Prevention of Chemotherapy-Induced Peripheral Neuropathy

“…Through a different mechanism, but with the ultimate downstream effect on the NF-kB pathway, nicotine is under investigation as another potential therapeutic strategy for both prevention and treatment of paclitaxel-induced CIPN (46). Associated data suggest that targeting the nicotinic acetylcholine receptormediated pathways may be promising for the prevention and treatment of CIPN induced by paclitaxel or oxaliplatin (47). A primary concern is that nicotine may also stimulate tumor growth, although the evidence for tumor proliferation has been inconsistent in preclinical models (47).…”

“…Associated data suggest that targeting the nicotinic acetylcholine receptormediated pathways may be promising for the prevention and treatment of CIPN induced by paclitaxel or oxaliplatin (47). A primary concern is that nicotine may also stimulate tumor growth, although the evidence for tumor proliferation has been inconsistent in preclinical models (47). Interestingly, smoking history has been classified as a risk factor for CIPN; however, this finding has limitations due to its determination from a secondary analysis whose primary endpoint was not related to this topic (48).…”

The Influence Dose of Nicotine Exposure on H520 Smoking-related Non-Small-Cell Lung Carcinoma Cell Growth and Toxicity

“…Among various subtypes of nicotinic receptors, α7nAChR, can bind nicotine with highest affinity and mediate multiple effects of nicotine in lung cancer. α7nAChR and EGFR expressed on lung carcinoma form a part of a proliferative network facilitating the growth of NSCLC cells [2]. Nicotine could induce the proliferation of a variety of lung carcinoma cell clines, but there is no evidence that nicotine itself provokes cancer.…”

“…The half-life of nicotine in human plasma is around 2 h[16,17]. The concentration of nicotine stimulated cell growth to correspond to low concentration was needed[18, 19]. Exposure to environmental nicotine have been shown to cause nephrotoxicity [20].…”