Activity of the MEK inhibitor selumetinib (AZD6244; ARRY-142886) in nasopharyngeal cancer cell lines.

Investigational New Drugs
B B Y MaA T C Chan

Abstract

This study evaluated the preclinical activity of selumetinib (AZD6244, ARRY-142866), an inhibitor of the mitogen-activated protein kinase kinase (MAPKK or MEK1/2) in 6 nasopharyngeal cancer (NPC) cell lines. Selumetinib could achieve up to 90 % inhibition of cell growth with the respective IC(50) values in NPC cell lines as follow: HK1 = 0.04 μM, HK1-LMP1(B95.8) = 0.17 μM, HONE-1-EBV = 0.46 μM, HONE-1 = 1.79 μM, CNE-2 = 2.20 μM and C666-1 > 10 μM. The drug-sensitive cell lines HK1, HK1-LMP1(B95.8) and HONE-1-EBV have higher basal expression of phosphorylated (pi)-MAPK than the less sensitive cell lines. BRAF mutations were not detected in all 6 cell lines. Re-introduction of the EBV genome into HONE-1 cells, generating the HONE-1-EBV cell line, seemed to result in elevated expression of pi-MAPK and sensitivity to selumetinib when compared with the parental HONE-1 cells. At a concentration of 0.5 μM and 5 μM, selumetinib induced apoptosis (as indicated by cleaved PARP expression and caspase 3 induction), and G(0)/G(1) cycle arrest in HONE-1-EBV and HK1-LMP1(B95.8) cells. The combination of selumetinib (at IC(25) concentration) and the EGFR tyrosine kinase inhibitor, gefitinib (at concentrations of 0.1, 3 and 9 μM) resulted in sy...Continue Reading

References

Nov 27, 2002·Seminars in Cancer Biology·Sai Wah TsaoDolly P Huang
May 15, 2003·Laboratory Investigation; a Journal of Technical Methods and Pathology·Angela Kwok Fung LoGeorge Sai Wah Tsao
Aug 23, 2005·International Journal of Cancer. Journal International Du Cancer·Yvonne Yan-Yan OrKwok-Wai Lo
Sep 20, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Muralidhar BeeramEric K Rowinsky
Nov 8, 2005·Nature·David B SolitNeal Rosen
Apr 14, 2006·Neoplasia : an International Journal for Oncology Research·Angela Kwok Fung LoDolly P Huang
Mar 3, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Tammie C YehEli Wallace
Jul 13, 2007·Journal of Virology·Bernardo A MainouNancy Raab-Traub
Jan 4, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Nikolas K HaassKeiran S M Smalley
Jan 18, 2008·Journal of Virology·Christopher W DawsonLawrence S Young
Aug 30, 2008·The Journal of Clinical Investigation·Arkaitz CarracedoPier Paolo Pandolfi
Mar 30, 2011·Cancer Research·Bingbing DaiJack A Roth
May 24, 2011·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Qiang ZuoWangjun Liao

❮ Previous
Next ❯

Citations

Nov 13, 2012·Investigational New Drugs·Brigette B Y MaAnthony T C Chan
Apr 8, 2016·Expert Opinion on Investigational Drugs·Paolo Bossi, Salvatore Alfieri
Sep 29, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ying Cheng, Hongqi Tian

❮ Previous
Next ❯

Related Concepts

Related Feeds

Anthelmintics

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.

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