Premium
Flavopiridol's effects on metastasis in KRAS mutant lung adenocarcinoma cells
Author(s) -
Dogan Turacli Irem,
Demirtas Korkmaz Funda,
Candar Tuba,
Ekmekci Abdullah
Publication year - 2019
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.27846
Subject(s) - kras , mutant , cancer research , adenocarcinoma , metastasis , biology , medicine , cancer , genetics , gene , colorectal cancer
Abstract Background There is still no clinically approved agent for mutant KRAS, which is the most common alteration in non–small‐cell lung cancer (NSCLC). Flavopiridol is a semisynthetic flavonoid that inhibits cell growth through cyclin‐dependent kinases in G1/S or G2/M of the cell cycle and induces apoptosis. In this study, we evaluated its effect on cellular apoptosis, survival, and metastasis mechanisms on KRAS mutant A549, Calu‐1, and H2009 cell lines. Methods The cytotoxic effects of flavopiridol on NSCLC cells were determined by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide cell viability test. The cells were treated with 200 and 400 nM flavopiridol, and, then, apoptosis, survival, and metastasis‐related protein expressions were determined by Western blot analysis. The antimetastatic effects of flavopiridol were assessed by wound healing and Galectin‐3 activity assay. Results Flavopiridol drastically affected toxicity in all KRAS mutant NSCLC cells at nanomolar concentrations. Also, it could efficiently inhibit wound healing and Galectin‐3 activity in all the cells tested. However, the metastasis‐related protein expressions did not reflect these obvious effects on blotting. p‐Erk was activated as a cellular survival mechanism to escape apoptosis in all the cells tested. Conclusion Although there are many mechanisms that still need to be elucidated, flavopiridol can be used as a metastasis inhibitor and an apoptosis inducer in KRAS mutant NSCLC.