Nicotinic acetylcholine receptors in chemotherapeutic drugs resistance: An emerging targeting candidate

Nour, Mina Afrashteh; Hajiasgharzadeh, Khalil; Kheradmand, Fatemeh; Asadzadeh, Zahra; Bolandi, Nadia; Baradaran, Behzad

doi:10.1016/j.lfs.2021.119557

Cited by 13 publications

(6 citation statements)

References 101 publications

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“…Pyrimidine antagonist-antimetabolite with a similar structure to naturally occurring compounds that are required for the viability and division of a cell; it inhibits the replication or the repair of DNA [87,88] Hydroxyurea Inhibits ribonucleotide reductase and blocks the formation of nucleotides needed for DNA synthesis and repair [87] Methotrexate Folate antagonist; it inhibits dihydrofolate reductase, affecting the de novo synthesis of purines used in DNA replication [87,89] Capecitabine Similar mechanism with 5-fluorouracil [87] Doctors observed that smoking cancer patients have lower chemotherapy response rates, mainly due to nicotine's ability to inhibit apoptosis and induce chemoresistance in cancer cells. Nicotine inhibited the apoptotic effect of cisplastin, vinblastine, paclitaxel, and doxorubicin [60,90].…”

Section: -Flurouracilmentioning

confidence: 96%

“…In the cells, nAchRs are located at two levels: on the cell membrane and the mitochondrial membrane [57]. α7 is the main subunit that mediates the proliferative effects of nicotine and the development of α7 nAchR antagonists can become a target for cancer therapy, but also for enhancing the therapeutic effect of anticancer drugs, nicotine exposure reducing apoptosis in cancer cells treated with different chemotherapy agents [57][58][59][60].…”

Section: Nicotinementioning

confidence: 99%

“…NNK and NNN, similar to nicotine, have the ability to activate nicotinic acetylcholine receptors (nAChRs), which plays an important role in cancer initiation, but also in chemoresistance [60]. Goniewicz et al analyzed the tobacco nitrosamines in the vapors generated from 12 brands of e-cigarettes and determined the concentrations of NNK and NNN per e-cigarette (150 puffs).…”

Section: Tobacco-specific Nitrosaminesmentioning

confidence: 99%

“…α7-AChRs were also involved in cancer cell survival and cisplatin resistance [62], and the involvement of α7 subunit of nAChR can be used to increase the effect of chemotherapy because adding α7 antagonists to the treatment of cancer patients could improve the anti-proliferative effect [57,60].…”

Section: -Flurouracilmentioning

confidence: 99%

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Electronic Cigarettes’ Toxicity: From Periodontal Disease to Oral Cancer

et al. 2021

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Electronic nicotine delivery systems first appeared on the market in 2003 and have been promoted as healthier alternatives to conventional tobacco cigarettes. The rapid evolution of technology for these products generated a wide variety of models, and electronic cigarettes have quickly gained worldwide popularity. However, research regarding the effects of both short-term and long-term exposure revealed a wide variety of potential negative effects on human health, and the first system to be affected by these electronic smoking devices is the oral cavity. This review makes an up-to-date extensive presentation of the possible mechanisms that associate electronic cigarette smoking with increased prevalence and progression of oral cancer. Oxidative stress, inflammation response, and DNA damage are the main mechanisms that explain e-cigarettes’ cytotoxicity, but there are still questions to be answered. At present, tens of thousands of e-liquids are available, with distinct compositions, which makes the research even more challenging. Another aspect approached in the present paper is the effect of nicotine on chemotherapy drug resistance. Nicotine activates nicotinic acetylcholine receptors, consecutively inhibiting apoptosis, increasing tumor cells proliferation and survival, and reducing the effects of chemotherapy drugs.

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Section: -Flurouracilmentioning

confidence: 96%

Section: Nicotinementioning

confidence: 99%

Section: Tobacco-specific Nitrosaminesmentioning

confidence: 99%

Section: -Flurouracilmentioning

confidence: 99%

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Electronic Cigarettes’ Toxicity: From Periodontal Disease to Oral Cancer

et al. 2021

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“…Activation of α7-nAChRs promotes growth and metastasis of pancreatic ductal adenocarcinomas ( Schaal et al, 2015 ), proliferation and invasion of breast ( Dasgupta et al, 2009 ), hepatocellular ( Li et al, 2019 ), gastric ( Tu et al, 2016 ), lung ( Davis et al, 2009 ; Wang and Hu, 2018 ), and glioblastoma ( Pucci et al, 2021 ) tumor cells. Activation of α7-nAChR also reduces efficiency of chemotherapy in lung, oral, breast, and gastric cancers ( Tu et al, 2016 ; Cheng et al, 2020 ; Afrashteh Nour et al, 2021 ). This receptor can form complexes with receptor tyrosine kinases (RTKs) such as epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor (PDGFR) and inositol-1,4,5-trisphosphate 3-kinase (IP3K) ( Chernyavsky et al, 2015 ; Bychkov et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Selective targeting of α7 nicotinic acetylcholine receptor by synthetic peptide mimicking loop I of human SLURP-1 provides efficient and prolonged therapy of epidermoid carcinoma in vivo

Shlepova,

Shulepko,

Shipunova

et al. 2023

Front. Cell Dev. Biol.

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α7-Type nicotinic acetylcholine receptor (α7-nAChR) promotes the growth and metastasis of solid tumors. Secreted Ly6/uPAR-Related Protein 1 (SLURP-1) is a specific negative modulator of α7-nAChR produced by epithelial cells. Here, we investigated mechanisms of antiproliferative activity of recombinant SLURP-1 in epidermoid carcinoma A431 cells and activity of SLURP-1 and synthetic 21 a.a. peptide mimicking its loop I (Oncotag) in a xenograft mice model of epidermoid carcinoma. SLURP-1 inhibited the mitogenic pathways and transcription factors in A431 cells, and its antiproliferative activity depended on α7-nAChR. Intravenous treatment of mice with SLURP-1 or Oncotag for 10 days suppressed the tumor growth and metastasis and induced sustained changes in gene and microRNA expression in the tumors. Both SLURP-1 and Oncotag demonstrated no acute toxicity. Surprisingly, Oncotag led to a longer suppression of pro-oncogenic signaling and downregulated expression of pro-oncogenic miR-221 and upregulated expression of KLF4 protein responsible for control of cell differentiation. Affinity purification revealed SLURP-1 interactions with both α7-nAChR and EGFR and selective Oncotag interaction with α7-nAChR. Thus, the selective inhibition of α7-nAChRs by drugs based on Oncotag may be a promising strategy for cancer therapy.

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