p38 mitogen‐activated protein kinase signaling, ERCC1 expression, and viability of lung cancer cells from never or light smoker patients

Abstract

BACKGROUND: Expression of DNA‐repair proteins and activated mitogen‐activated protein kinases (MAPKs) may differ according to smoking status. The authors investigated whether p38 MAPK activity contributed to the viability of cisplatin in lung cancer cell lines from never or light smokers and to ERCC1 mRNA expression. METHODS: Activated p38 MAPK was tested as a predictor for ERCC1 levels in 117 lung adenocarcinomas. Cell viabilities of NCI‐H1975, NCI‐H1793, NCI‐H1650, and NCI‐H1651 cell lines, derived from never or light smokers, were measured after treatment with the p38 MAPK inhibitor SB202190 and cisplatin. The role of p38α (MAPK14) and p38β (MAPK11) isoforms and ERCC1 was evaluated using RNA interference. RESULTS: ERCC1 protein‐level expression was predicted by activated p38 MAPK in lung adenocarcinoma tissues. The p38‐specific inhibitor SB202190 strongly decreased cell viability (43%‐63%). SB202190 plus cisplatin significantly decreased cell viability in every cell line, including cisplatin‐resistant NCI‐H1793. Genetic inhibition, targeting both MAPK11 and MAPK14, reduced the viability of the different cell lines: down‐regulation of p38β accounted for most of this effect. Cisplatin's effect was greater after MAPK11 down‐regulation for NCI‐H1651, and MAPK14 down‐regulation for NCI‐H1650. In addition, both SB202190 and MAPK11 inhibition reduced excision repair cross‐complementing 1 mRNA levels. CONCLUSIONS: Lung cancer cells from never or light smokers rely on p38 MAPK signaling for survival. MAPK11 is involved in that pathway and might contribute to ERCC1 expression. Sensitization to cisplatin can be achieved by pharmacological inhibition of p38 MAPK signaling. Cancer 2012. © 2012 American Cancer Society.

Asiatic Acid, Extracted from Centella asiatica and Induces Apoptosis Pathway through the Phosphorylation p38 Mitogen-Activated Protein Kinase in Cisplatin-Resistant Nasopharyngeal Carcinoma Cells

“…Related researches mention that AA cause activation of mitochondrial pathway via regulating B cell CLL/lymphoma 2 (BCL2) family proteins and increasing the ratio of Bax to Bcl2 which lead to cancer cell apoptosis [19,20]. Previous studies revealed that the AA-induced apoptosis of human cancer cell is mediated by the mitogen-activated protein kinase (MAPK) pathway with or without involving the activated caspases [5,6,21]. The inhibition of ERK and p38 phosphorylation in AA-treated cancer cell are also noted [15].…”

“…Liu et al proposed that the resistance might be sensitized by increasing Bax/Bcl-2 mRNA ratios caused by inhibited NFκB expression and downregulating ERCC1 and thymidine phosphorylase (TP) by inhibiting the phosphorylation of ERK, p38 and PI3K/AKT pathways, which all lead to apoptosis, in human hepatoma HepG2 cells [23]. Another research also revealed the decreased ERCC1 mRNA expression by downregulation of p38 MAPK pathway [21]. Consistent with these studies, our results revealed significantly increased expression of Bax and decreased phosphorylation of ERK in AA-treated cis-NPC cell lines.…”

A Quest for miRNA Bio-Marker: A Track Back Approach from Gingivo Buccal Cancer to Two Different Types of Precancers

“…As of now, functional role of hsa-miR-1293 in cancer is very limited. According to miRWalk [21] and StarBase [33], one of the predicted targets of hsa-miR-1293 is MAPK14 (p38) which has been shown to be associated with tumor's sensitivity to cis -platinum treatment [34]. If this predicted relationship could be validated, then expression of this miRNA may be useful in prediction of patient's sensitivity to cis -platinum treatment.…”

Smoking Induces Epithelial-to-Mesenchymal Transition in Non–Small Cell Lung Cancer through HDAC-Mediated Downregulation of E-Cadherin

“…2A). In addition to E-cadh (34), alterations in other factors like p38MAPK (35), twist (36), cyclin D1 (37) and DNA repair capacity (38) are also involved in smoking related reduced survival in cancer patients. Our results reveal, for the first time, that smoking-mediated decrease in E-cadh expression plays a key role in the induction in EMT in lung cancer.…”