APS8, a Polymeric Alkylpyridinium Salt Blocks α7 nAChR and Induces Apoptosis in Non-Small Cell Lung Carcinoma

Zovko, Ana; Viktorsson, Kristina; Lewensohn, Rolf; Kološa, Katja; Filipič, Metka; Xiao, Hong; Kem, William R.; Paleari, Laura; Turk, Tom

doi:10.3390/md11072574

Cited by 29 publications

(52 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Based on this information, α7nAChRs antagonists were revealed to attenuate the proliferative effects of nicotine in lung cancer (22). An analog of 3-alkylpyridinium polymers with a defined alkyl chain length and molecular size (APS8) may inhibit tumor may inhibit tumor growth and trigger the intrinsic apoptotic pathways in NSCLCs (55). Another study has confirmed that α7nAChRs antagonists including d-tubocurarine and α-cobratoxin (α-CbT) may reduce tumor cell growth factors stimulated by Table I.…”

Section: Function and Mechanisms Of α7nachr On Cell Proliferationmentioning

confidence: 97%

“…Nicotine may also induce NSCLC cells invasion, migration and mesenchymal transition, which were mediated by α7nAChR involving the MEK/ERK signaling pathway (27). Meanwhile, the effects induced by nicotine may be suppressed by pharmacological intervention using α7nAChR selective antagonists or by genetic intervention using α7nAChR small interfering RNAs (55,68). α-bungarotoxin appeared to be one of the specific inhibitor for α7nAChR, which blocked metastatic tumors by NNK-induced tyrosine phosphorylation of proto-oncogene tyrosine-protein kinase Src, protein kinase Cι and focal adhesion kinase (65).…”

Section: Function and Mechanisms Of α7nachr On Metastasismentioning

confidence: 99%

See 1 more Smart Citation

α7 nicotinic acetylcholine receptors in lung cancer (Review)

Wang

2018

Oncol Lett

View full text Add to dashboard Cite

Abstract. Lung cancer has one of the highest mortality rates among malignancies globally, and smoking has been documented as the main cause of lung cancer. Nicotinic acetylcholine receptors (nAChRs) were initially identified as notable regulators of the nervous system. In addition to their function in the brain, accumulating evidence indicates that nAChRs perform a host of diverse functions in almost all non-neuronal mammalian cells. The homomeric α7nAChR, a subtype of nAChRs, is responsible for the proliferative, pro-angiogenic and pro-metastatic effects of nicotine in lung cancer. Provided the association of cigarette smoking with several disease types such as cardiovascular disease, the α7nAChR-mediated signaling pathway has been implicated in the pathophysiology of lung cancer. Currently, strategies that target the α7nAChR including α7nAChR antagonists are considered to be potentially useful anticancer drugs for therapeutic purposes. Thus, the present review assesses current understanding of the function and underlying molecular mechanisms of α7nAChR in lung cancer and evaluates how targeting α7nAChR may result in novel therapeutic methods. IntroductionLung cancer is one of the most commonly occurring carcinoma types globally and has limited treatment options for advanced-stage disease (1). Lung cancer is a heterogeneous disease comprised of two main pathological types: Non-small-cell lung cancer (NSCLC) which accounts for 70-80% of all lung cancer cases and small-cell lung cancer (SCLC) which accounts for ~20% of all lung cancer cases (2). NSCLCs may be divided into three subtypes: Squamous-cell carcinoma (25-30% of all lung cancer cases), adenocarcinoma (~40% of all lung cancer cases) and large-cell carcinoma (10-15% of all lung cancer cases) (3). SCLC is the second most prevalent form of lung cancer, with a 5-year survival rate of <7% (4). Cigarette smoking is considered to be the main risk factor for lung cancer, and ~90% of all cases are associated with exposure to smoking and second-hand smoking (5). Other contributory factors include residential radon, occupational hazards including exposure to asbestos, arsenic and polycyclic aromatic hydrocarbons, radiation, coal smoke, indoor emission of fuel burning, outdoor pollution, previous non-malignant lung diseases in addition to a family history of tumors (6,7). Squamous-cell, large-cell and SCLC are the most commonly identified types of lung cancer present in smokers (8,9). In contrast, adenocarcinoma is the lung cancer type most commonly identified in non-smokers (10).Cigarette smoke is a mixture of thousands of chemical compounds, a number of which have potent carcinogenic potential including polycyclic aromatic hydrocarbons, nicotine and the nicotine-derived nitrosamines 4-(methylnitrosamino)-1-(3-pyrydyl)-1-butanone (NNK) and N-nitrosonornicotine (11). The most harmful and addictive component is nicotine (11). These carcinogens and their metabolites may induce the formation of DNA adducts which result in mutations of a number of key cancer suppressor...

show abstract

Section: Function and Mechanisms Of α7nachr On Cell Proliferationmentioning

confidence: 97%

Section: Function and Mechanisms Of α7nachr On Metastasismentioning

confidence: 99%

α7 nicotinic acetylcholine receptors in lung cancer (Review)

Wang

2018

Oncol Lett

View full text Add to dashboard Cite

show abstract

“…α-Cobratoxin, a high-affinity α7-nAChR antagonist reduced tumor growth in nude mice orthotopically engrafted with NSCLC cells [59]. An α7nAChR inhibitor (APS8) may suppress NSCLCs proliferative effects of nicotine [58]. These studies revealed that nicotine/α7nAChR signals mediate proliferation in lung cancer.…”

Section: Cell Proliferationmentioning

confidence: 99%

“…α7nAChR levels in patients with SCC who are active smokers are correlated with their smoking history [31]. The function of α7nAChR-mediated lung cancer progression including in proliferation [31,[54][55][56][57][58][59][60][61][62][63][64][65], angiogenesis [66], and metastasis [39,[67][68][69], has been revealed (Fig. 2).…”

Section: The Potential Mechanisms Of Nicotine On Lung Cancer Progressionmentioning

confidence: 99%

Nicotinic-nAChR signaling mediates drug resistance in lung cancer

Cheng

Chen

Lee³

et al. 2020

J. Cancer

View full text Add to dashboard Cite

Lung cancer is the leading cause of cancer death worldwide. Cigarette smoking is the most common risk factor for lung carcinoma; other risks include genetic factors and exposure to radon gas, asbestos, secondhand smoke, and air pollution. Nicotine, the primary addictive constituent of cigarettes, contributes to cancer progression through activation of nicotinic acetylcholine receptors (nAChRs), which are membrane ligand-gated ion channels. Activation of nicotine/nAChR signaling is associated with lung cancer risk and drug resistance. We focused on nAChR pathways activated by nicotine and its downstream signaling involved in regulating apoptotic factors of mitochondria and drug resistance in lung cancer. Increasing evidence suggests that several sirtuins play a critical role in multiple aspects of cancer drug resistance. Thus, understanding the consequences of crosstalk between nicotine/nAChRs and sirtuin signaling pathways in the regulation of drug resistance could be a critical implication for cancer therapy.

show abstract

“…Our overall results are in line with studies investigating the cytotoxicity of nicotine in various in vitro systems. Nicotine, at a concentration of 1μM, was shown to exert a minor effect on the viability of MRC-5 normal fibroblasts, while the proliferation of both human lung cancer cell lines A549 and SKMES-1 (13% for A549 and 14% for SKMES-1) was slightly enhanced (22). The treatment of MRC-5 cells with nicotine-free tobacco extract (1 mg/mL, but no 0.1 mg/mL) reduced (p < 0.05) the viability of MRC-5 cells by 42%, indicating that components other than nicotine in tobacco leaves exhibited cytotoxic effect (23).…”

mentioning

confidence: 96%

Comparative cytotoxicity study of nicotine and cotinine on MRC-5 cell line

Vlasceanu¹,

Baconi²,

Gălățeanu³

et al. 2018

JMMS

View full text Add to dashboard Cite

Nicotine has several health hazards regarding carcinogenic potential. It also imparts increased risk for respiratory, cardiovascular, and gastrointestinal disorders. Several mechanisms have been proposed for the carcinogenic potential, including effects on cell proliferation, inducing oxidative stress, DNA mutation, or inhibition of apoptosis. The cotinine metabolite is generally thought to have effects similar to nicotine in some experimental systems. The purpose of this study was to assess the nicotine and cotinine cytotoxicity on MRC-5 lung fibroblasts. The pulmonary fibroblasts were treated with various concentrations of nicotine or cotinine (in the range 1 µM-2 mM) for 24 or 48 h and analyzed for cell viability by MTT test. The results indicated that high nicotine concentrations (2 mM) induced marked cell death (about 50%) in MRC-5 cell line. Cotinine showed lower toxicity than nicotine on the MRC-5 cells. In contrast to nicotine treatment, cells treated with cotinine continued to proliferate after the 48h incubation period.

show abstract

APS8, a Polymeric Alkylpyridinium Salt Blocks α7 nAChR and Induces Apoptosis in Non-Small Cell Lung Carcinoma

Cited by 29 publications

References 52 publications

α7 nicotinic acetylcholine receptors in lung cancer (Review)

α7 nicotinic acetylcholine receptors in lung cancer (Review)

Nicotinic-nAChR signaling mediates drug resistance in lung cancer

Comparative cytotoxicity study of nicotine and cotinine on MRC-5 cell line

Contact Info

Product

Resources

About