Targeting alpha7-nicotinic receptor for the treatment of pleural mesothelioma

European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)
A CatassiP Russo

Abstract

Human malignant pleural mesothelioma (MPM) is a dreadful disease and there is still no standard therapy available for a consistent therapeutic approach. This research is aimed at the evaluation of the potential therapeutic effect of a specific nicotinic receptor (nAChR) antagonist, namely alpha-Cobratoxin (alpha-CbT). Its effectiveness was tested in mesothelioma cell lines and in primary mesothelioma cells in vitro, as well as in vivo, in orthotopically xenotransplanted NOD/SCID mice. Cells showed alpha7-nAChR expression and their growth was significantly inhibited by alpha-CbT. Severe induction of apoptosis was observed after exposure to alpha-CbT [IC(80-90)]. Apoptosis was characterised by: change in mitochondrial potential, caspase-3 cleavage, down-regulation of mRNA and protein for survivin, XIAP, IAP1, IAP2 and Bcl-XL, inhibition by caspase-3 inhibitor. In vivo, the alpha-CbT acute LD(50) was 0.15 mg/kg. The LD(100) [0.24 mg/kg] induced fatal respiratory failure and massive kidney necrosis. Phase II experiments with 0.12 ng/kg alpha-CbT (1/1000 of LD(10)) were done in 53 xenotransplanted mice, inhibiting tumour development as confirmed by chest X-ray examinations, autopsy and microscopical findings. The growth of human pro...Continue Reading

References

May 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·R Maneckjee, J D Minna
Jul 15, 1971·European Journal of Biochemistry·E KarlssonD Eaker
Dec 1, 1984·Cancer Letters·P RussoG Vidali
Oct 4, 2003·Nature Reviews. Drug Discovery·Richard J Lewis, Maria L Garcia
Apr 15, 2005·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Monica FalleniSilvano Bosari
Sep 20, 2005·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·A KlabatsaD A Fennell
Mar 15, 2006·Critical Reviews in Clinical Laboratory Sciences·Hellinida Thomadaki, Andreas Scorilas
Apr 8, 2006·Proceedings of the National Academy of Sciences of the United States of America·Piyali DasguptaSrikumar Chellappan
May 8, 2007·Cell·Brian Keith, M Celeste Simon
Dec 11, 2007·International Journal of Cancer. Journal International Du Cancer·Alessia GrozioPatrizia Russo
Feb 12, 2008·Seminars in Cancer Biology·Laura PaleariPatrizia Russo

❮ Previous
Next ❯

Citations

May 5, 2011·Journal of Oncology·Sandeep SinghSrikumar Chellappan
Jan 20, 2009·American Journal of Respiratory and Critical Care Medicine·Laura PaleariMassimo Fini
Jun 6, 2009·American Journal of Respiratory and Critical Care Medicine·Eliot R Spindel
Apr 30, 2009·The International Journal of Biochemistry & Cell Biology·Hugo R AriasShaker A Mousa
Mar 28, 2009·International Journal of Cancer. Journal International Du Cancer·Laura PaleariPatrizia Russo
May 16, 2014·Nature Reviews. Cancer·Sergei A Grando
Nov 10, 2011·Toxins·Adak NasiripourdoriAntoine Taly
Sep 22, 2017·The Journal of Veterinary Medical Science·Taiki MiharaMasatoshi Hori
Jan 9, 2014·Molecular Cancer Research : MCR·Courtney Schaal, Srikumar P Chellappan
Aug 1, 2009·Archives of Pathology & Laboratory Medicine·Ilyssa O GordonAliya N Husain

❮ Previous
Next ❯

Related Concepts

Related Feeds

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis