Nicotine inhibits MAPK signaling and spheroid invasion in ovarian cancer cells.

Nicotine inhibits MAPK signaling and spheroid invasion in ovarian cancer cells. Exp Cell Res. 2020 Jul 07;:112167 Authors: Harmych SJ, Kumar J, Bouni ME, Chadee DN Abstract Nicotine is the major addictive component of cigarette smoke and although it is not considered carcinogenic, it can enhance or inhibit cancer cell proliferation depending on the type of cancer. Nicotine mediates its effects through nicotinic acetylcholine receptors (nAChRs), which are expressed in many different neuronal and non-neuronal cell types. We observed that the α4, α5, α7 subunits nAChRs were expressed in ovarian cancer (OC) cells. Nicotine inhibited the proliferation of SKOV3 and TOV112D OC cells, which have TP53 mutation and wild-type KRAS, but did not inhibit the proliferation of TOV21G or HEY OC cells, which have KRAS mutation and wild-type TP53. Exposure to nicotine for 96 h led to a significant reduction in the amounts of activated extracellular signal-regulated kinase (ERK) and activated p38 mitogen-activated protein kinases (MAPKs) in SKOV3 cells; and in activated ERK in TOV112D cells. In addition, SKOV3 and TOV112D invasion and spheroid formation was substantially inhibited by siRNA knockdown of mixed lineage kinase 3 (MLK3), or MEK inhibition. Nicotine treatment reduced SKOV3 and TOV112D spheroid invasion and compaction but did not significantly affect spheroid formation. Furthermore, SKOV3 spheroid invasion was blocked by p38 inhibition wi...
Source: Experimental Cell Research - Category: Cytology Authors: Tags: Exp Cell Res Source Type: research