Abstract
One of the earliest descriptions of non-neuronal ACh synthesis was by Morris who reported that ACh was synthesized in the placenta [1]; furthermore, Falugi et al. showed the presence of AChE in human fibrosarcoma cells [2]. Afterward, the expression of ACh, AChE, and cholinergic receptors in non-neuronal cells was reported in several studies [3-16]. Indeed, recent data reported that SCLC expresses a cholinergic autocrine loop that can regulate cell growth. Such work demonstrates that SCLC cells have a cholinergic phepotype and that ACh exerts as an autocrine growth factor in human lung tumours [16]. Moreover, it has been recently reported that nicotine in lung adenocarcinoma A549 cells, potently induces Bad phosphorylation at serine (S)112, S136 and S155 in a mechanism involving activation of MAPKs, ERK1/2, PI3K/AKT and PKA through the linking to α7-receptors [9]. Bad phosphorylation results in sequestering Bad from mitochondria and subsequently interacting with 14-3-3 in the cytosol [9]. We have recently reported that human malignant pleural mesothelioma expresses a cholinergic system, involved in cell growth regulation. Hence, mesothelioma cells growth is modulated by the cholinergic system in which agonists (i.e. nicotine) have a proliferative effect and antagonists (i.e. curare or α-cobratoxin) have an inhibitory effect. Furthermore apoptosis mechanisms, are under the control of the cholinergic system (nicotine antiapoptotic via induction of NF-κB complexes and phosphorylation of Bad at S112, curare proapoptotic via G0-G1, arrest p21waf-1-dependent, but p53-independent) [16]. The involvement of the non-neuronal cholinergic system in lung cancer and mesothelioma appears reasonable and opens up new translational research strategies.
| Original language | English |
|---|---|
| Pages (from-to) | 3493-3512 |
| Number of pages | 20 |
| Journal | Current Medicinal Chemistry |
| Volume | 13 |
| Issue number | 29 |
| DOIs | |
| Publication status | Published - Dec 2006 |
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Keywords
- Cell growth
- Lung cancer
- Mesothelioma
- Neurotoxins
- Non-neuronal cholinergic system
ASJC Scopus subject areas
- Organic Chemistry
- Biochemistry, Genetics and Molecular Biology(all)
- Biochemistry
- Pharmacology
Cite this
Development of novel therapeutic strategies for lung cancer : Targeting the cholinergic system. / Russo, Patrizia; Catassi, A.; Cesario, A.; Servent, D.
In: Current Medicinal Chemistry, Vol. 13, No. 29, 12.2006, p. 3493-3512.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Development of novel therapeutic strategies for lung cancer
T2 - Targeting the cholinergic system
AU - Russo, Patrizia
AU - Catassi, A.
AU - Cesario, A.
AU - Servent, D.
PY - 2006/12
Y1 - 2006/12
N2 - One of the earliest descriptions of non-neuronal ACh synthesis was by Morris who reported that ACh was synthesized in the placenta [1]; furthermore, Falugi et al. showed the presence of AChE in human fibrosarcoma cells [2]. Afterward, the expression of ACh, AChE, and cholinergic receptors in non-neuronal cells was reported in several studies [3-16]. Indeed, recent data reported that SCLC expresses a cholinergic autocrine loop that can regulate cell growth. Such work demonstrates that SCLC cells have a cholinergic phepotype and that ACh exerts as an autocrine growth factor in human lung tumours [16]. Moreover, it has been recently reported that nicotine in lung adenocarcinoma A549 cells, potently induces Bad phosphorylation at serine (S)112, S136 and S155 in a mechanism involving activation of MAPKs, ERK1/2, PI3K/AKT and PKA through the linking to α7-receptors [9]. Bad phosphorylation results in sequestering Bad from mitochondria and subsequently interacting with 14-3-3 in the cytosol [9]. We have recently reported that human malignant pleural mesothelioma expresses a cholinergic system, involved in cell growth regulation. Hence, mesothelioma cells growth is modulated by the cholinergic system in which agonists (i.e. nicotine) have a proliferative effect and antagonists (i.e. curare or α-cobratoxin) have an inhibitory effect. Furthermore apoptosis mechanisms, are under the control of the cholinergic system (nicotine antiapoptotic via induction of NF-κB complexes and phosphorylation of Bad at S112, curare proapoptotic via G0-G1, arrest p21waf-1-dependent, but p53-independent) [16]. The involvement of the non-neuronal cholinergic system in lung cancer and mesothelioma appears reasonable and opens up new translational research strategies.
AB - One of the earliest descriptions of non-neuronal ACh synthesis was by Morris who reported that ACh was synthesized in the placenta [1]; furthermore, Falugi et al. showed the presence of AChE in human fibrosarcoma cells [2]. Afterward, the expression of ACh, AChE, and cholinergic receptors in non-neuronal cells was reported in several studies [3-16]. Indeed, recent data reported that SCLC expresses a cholinergic autocrine loop that can regulate cell growth. Such work demonstrates that SCLC cells have a cholinergic phepotype and that ACh exerts as an autocrine growth factor in human lung tumours [16]. Moreover, it has been recently reported that nicotine in lung adenocarcinoma A549 cells, potently induces Bad phosphorylation at serine (S)112, S136 and S155 in a mechanism involving activation of MAPKs, ERK1/2, PI3K/AKT and PKA through the linking to α7-receptors [9]. Bad phosphorylation results in sequestering Bad from mitochondria and subsequently interacting with 14-3-3 in the cytosol [9]. We have recently reported that human malignant pleural mesothelioma expresses a cholinergic system, involved in cell growth regulation. Hence, mesothelioma cells growth is modulated by the cholinergic system in which agonists (i.e. nicotine) have a proliferative effect and antagonists (i.e. curare or α-cobratoxin) have an inhibitory effect. Furthermore apoptosis mechanisms, are under the control of the cholinergic system (nicotine antiapoptotic via induction of NF-κB complexes and phosphorylation of Bad at S112, curare proapoptotic via G0-G1, arrest p21waf-1-dependent, but p53-independent) [16]. The involvement of the non-neuronal cholinergic system in lung cancer and mesothelioma appears reasonable and opens up new translational research strategies.
KW - Cell growth
KW - Lung cancer
KW - Mesothelioma
KW - Neurotoxins
KW - Non-neuronal cholinergic system
UR - http://www.scopus.com/inward/record.url?scp=33845296073&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33845296073&partnerID=8YFLogxK
U2 - 10.2174/092986706779026192
DO - 10.2174/092986706779026192
M3 - Article
VL - 13
SP - 3493
EP - 3512
JO - Current Medicinal Chemistry
JF - Current Medicinal Chemistry
SN - 0929-8673
IS - 29
ER -