EGF-Dependent and Independent Programmed Cell Death Pathways in NCI-H596 Nonsmall Cell Lung Cancer Cells

Mcl-1 regulates survival and sensitivity to diverse apoptotic stimuli in human non-small cell lung cancer cells

“…Similar to other tumor models, we found that EGF can upregulate Mcl-1 levels which may at least in part explain previous reports demonstrating that overexpression of EGFR correlates with resistance to chemotherapy. 32,62,63 Consistent with reports showing the mitogen activated kinase pathway (MAP) can regulate Mcl-1 expression in response to EGF through AP-1 sites in the Mcl-1 promoter, we found that inhibition of ERK signaling prevents upregulation of Mcl-1 by EGF. 32 More work is required to fully understand both ligand-dependent and ligand-independent regulation of Mcl-1 in lung cancer cells.…”

Flavonoids as RTK inhibitors and potential anticancer agents

“…In pulmonary adenosquamous carcinoma NCI-H596 cells using [ 3 H] thymidine incorporation, Lei et al 72 showed that genistein at 93 mM inhibited DNA synthesis by 30% and that this effect on cell proliferation was dose and time-dependent. Furthermore, genistein (93 mM) (i) inhibited ERK2 kinase activity, (ii) attenuated EGFR and ERK phosphorylation in EGF-stimulated cells, and (iii) induced cross-linked envelope competence and DNA fragmentation, opening an apoptosis/death pathway in NSCLC cells.…”

Activation of Stat3 by receptor tyrosine kinases and cytokines regulates survival in human non-small cell carcinoma cells

“…First, tyrosine kinase growth factor receptors are overexpressed in a large number of human lung cancers, with non-small cell lung cancers demonstrating overexpression of EGF-R and its ligands EGF, amphiregulin, and TGF-alpha, while some small cell lung cancers demonstrate c-kit overexpression (Antoniades et al, 1992;Rusch et al, 1993Rusch et al, , 1997Takanami et al, 1995;Kawai et al, 1997;Krystal et al, 2000;Brabender et al, 2001). Lung cancer cell lines can produce soluble EGF or TGF-alpha and targeting the EGF-R with either monoclonal antibodies or small molecule inhibitors can lead to inhibition of tumor growth and in some cases tumor regression (Lee et al, 1992;Rabiasz et al, 1992;Lei et al, 1998Lei et al, , 1999Fang and Chen, 1999;Ciardiello et al, 2000;Sirotnak et al, 2000;Wang et al, 2000a;Norman, 2001). Second, Src, a major upstream regulator of STAT activity, has also been suggested to be activated in human lung cancers (Mazurenko et al, 1992;Budde et al, 1994).…”