Tags

Type your tag names separated by a space and hit enter

Effects of CAY10404 on the PKB/Akt and MAPK pathway and apoptosis in non-small cell lung cancer cells.
Respirology. 2009 Aug; 14(6):850-8.R

Abstract

BACKGROUND AND OBJECTIVE

Lung cancer is the most common cause of cancer death in men and women worldwide. The mechanism of cell death induced by CAY10404, a highly selective cyclooxygenase-2 inhibitor, was evaluated in three non-small cell lung cancer (NSCLC) cell lines (H460, H358, H1703).

METHODS

To measure the effects of CAY10404 on proliferation of NSCLC cells, 3 x 10(3) cells/well were plated in 96-well plates and allowed to adhere overnight at 37 degrees C. After treatment with CAY10404 for 3 days, cell proliferation was measured by the 3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In the H460 NSCLC cells, evidence of apoptosis was sought using the terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labelling (TUNEL) assay and western blot analysis.

RESULTS

Treatment with CAY10404 in the range of 10-100 microM caused dose-dependent growth inhibition, with an average 50% inhibitory concentration (IC(50)) of 60-100 micromol/L, depending on the cell line. Western blot analysis of CAY10404-treated cells showed cleavage of poly (ADP-ribose) polymerase (PARP) and procaspase-3, signifying caspase activity and apoptotic cell death. CAY10404 treatment inhibited the phosphorylation of Akt, glycogen synthase kinase-3beta and extracellular signal-regulated kinases 1/2 in H460 and H358 cells.

CONCLUSIONS

These results suggest that CAY10404 is a potent inducer of apoptosis in NSCLC cells, and that it may act by suppressing multiple protein kinase B/Akt and mitogen-activated protein kinase pathways.

Authors+Show Affiliations

Department of Internal Medicine, Medical Sciences Research Institute, School of Medicine, Eulji University, Jung-Gu, Daejeon, Republic of Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19703066

Citation

Cho, Yongseon, et al. "Effects of CAY10404 On the PKB/Akt and MAPK Pathway and Apoptosis in Non-small Cell Lung Cancer Cells." Respirology (Carlton, Vic.), vol. 14, no. 6, 2009, pp. 850-8.
Cho Y, Park MJ, Park M, et al. Effects of CAY10404 on the PKB/Akt and MAPK pathway and apoptosis in non-small cell lung cancer cells. Respirology. 2009;14(6):850-8.
Cho, Y., Park, M. J., Park, M., Min, S. S., Yee, J., Kim, C., Han, M. S., & Han, S. H. (2009). Effects of CAY10404 on the PKB/Akt and MAPK pathway and apoptosis in non-small cell lung cancer cells. Respirology (Carlton, Vic.), 14(6), 850-8. https://doi.org/10.1111/j.1440-1843.2009.01563.x
Cho Y, et al. Effects of CAY10404 On the PKB/Akt and MAPK Pathway and Apoptosis in Non-small Cell Lung Cancer Cells. Respirology. 2009;14(6):850-8. PubMed PMID: 19703066.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of CAY10404 on the PKB/Akt and MAPK pathway and apoptosis in non-small cell lung cancer cells. AU - Cho,Yongseon, AU - Park,Mee-Ja, AU - Park,Mira, AU - Min,Sun Seek, AU - Yee,Jaeyong, AU - Kim,Chan, AU - Han,Min-Soo, AU - Han,Seung-Ho, PY - 2009/8/26/entrez PY - 2009/8/26/pubmed PY - 2009/12/22/medline SP - 850 EP - 8 JF - Respirology (Carlton, Vic.) JO - Respirology VL - 14 IS - 6 N2 - BACKGROUND AND OBJECTIVE: Lung cancer is the most common cause of cancer death in men and women worldwide. The mechanism of cell death induced by CAY10404, a highly selective cyclooxygenase-2 inhibitor, was evaluated in three non-small cell lung cancer (NSCLC) cell lines (H460, H358, H1703). METHODS: To measure the effects of CAY10404 on proliferation of NSCLC cells, 3 x 10(3) cells/well were plated in 96-well plates and allowed to adhere overnight at 37 degrees C. After treatment with CAY10404 for 3 days, cell proliferation was measured by the 3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In the H460 NSCLC cells, evidence of apoptosis was sought using the terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labelling (TUNEL) assay and western blot analysis. RESULTS: Treatment with CAY10404 in the range of 10-100 microM caused dose-dependent growth inhibition, with an average 50% inhibitory concentration (IC(50)) of 60-100 micromol/L, depending on the cell line. Western blot analysis of CAY10404-treated cells showed cleavage of poly (ADP-ribose) polymerase (PARP) and procaspase-3, signifying caspase activity and apoptotic cell death. CAY10404 treatment inhibited the phosphorylation of Akt, glycogen synthase kinase-3beta and extracellular signal-regulated kinases 1/2 in H460 and H358 cells. CONCLUSIONS: These results suggest that CAY10404 is a potent inducer of apoptosis in NSCLC cells, and that it may act by suppressing multiple protein kinase B/Akt and mitogen-activated protein kinase pathways. SN - 1440-1843 UR - https://www.unboundmedicine.com/medline/citation/19703066/Effects_of_CAY10404_on_the_PKB/Akt_and_MAPK_pathway_and_apoptosis_in_non_small_cell_lung_cancer_cells_ L2 - https://doi.org/10.1111/j.1440-1843.2009.01563.x DB - PRIME DP - Unbound Medicine ER -