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Non-small cell lung cancer (NSCLC) harboring activating EGFR mutations were initially treated by first-generation EGFR tyrosine kinase inhibitors (EGFR-TKIs), unfortunately, the efficacy of these drugs is limited, mostly frequent due to T790M mutation. Although osimertinib has been approved to treat patients with T790M-positive NSCLC, the majority of patients will develop C797S mutation and suffer diseases again. Therefore, more novel therapeutic strategies for T790M mutation-positive NSCLC are urgently required. We hypothesized that wighteone, a natural compound isolated from plant derivatives, has antitumor effects against NSCLC with T790M mutation. In this study, we created a Ba/F3 cell line harboring EGFR L858R/T790M mutation (Ba/F3 EGFR L858R/T790M cell line), and then used this cell line and a human NSCLC cell line with EGFR L858R/T790M mutation (NCI-H1975) to investigate the effects and mechanism of wighteone. The results showed that wighteone inhibited cell proliferation, suppressed EGFR signaling pathway, caused cell cycle redistribution and induced cell apoptosis. Our studies suggest that wighteone may provide a novel potential therapeutic strategy for NSCLC patients with T790M mutation.

Wighteone exhibits an antitumor effect against EGFR L858R/T790M mutation non-small cell lung cancer