Heterogeneous Off-Target Effects of Ultra-Low Dose Dimethyl Sulfoxide (DMSO) on Targetable Signaling Events in Lung Cancer In Vitro Models.

ABSTRACT: Targetable alterations in cancer offer novel opportunities to the drug discovery process. However, pre-clinical testing often requires solubilization of these drugs in cosolvents like dimethyl sulfoxide (DMSO). Using a panel of cell lines commonly used for in vitro drug screening and pre-clinical testing, we explored the DMSO off-target effects on functional signaling networks, drug targets, and downstream substrates. Eight Non-Small Cell Lung Cancer (NSCLC) cell lines were incubated with three concentrations of DMSO (0.0008%, 0.002%, and 0.004% v/v) over time. Expression and activation levels of 187 proteins, of which 137 were kinases and downstream substrates, were captured using the Reverse Phase Protein Array (RPPA). The DMSO effect was heterogeneous across cell li

SUBMITTER: Baldelli E 

PROVIDER: S-EPMC8001778 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature