Picropodophyllotoxin Inhibits Cell Growth and Induces Apoptosis in Gefitinib-Resistant Non-Small Lung Cancer Cells by Dual-Targeting EGFR and MET

Abstract

Picropodophyllotoxin (PPT) is an epimer of podophyllotoxin (PT), which is a bitter-tasting aryltetralin-type lignan and was the main component in the alcohol-soluble fraction of Podophyllum species (Canel et al., 2000;Gordaliza et al., 2004;Shah et al., 2021). PT targets microtubule assembly and exhibits potent anticancer activity but has severe systemic toxicity in normal cells (Gordaliza et al., 2004;Zhao et al., 2021). Thus, PPT with a low toxicity, 50% lethal dose (LD50) of more than 500 mg/kg in rodents was developed (Girnita et al., 2004;Vasilcanu et al., 2004). Interestingly, despite its high structural

Anthriscus sylvestris—Noxious Weed or Sustainable Source of Bioactive Lignans?

“…While tyrosine kinase inhibitors (TKIs) like gefitinib are the mainstay treatment for NSCLC patients with epidermal growth factor receptor (EGFR) amplification or sensitive mutations, the majority inevitably encounter disease progression as a result of acquired resistance to these agents. Resistance mechanisms often involve modifications in EGFR or its downstream pathways, underscoring the need for intensified clinical investigation into innovative agents that target prevalent resistance pathways, such as mesenchymal–epithelial transition (MET) expression [ 152 , 153 , 154 ].…”

“…This inhibition resulted in decreased phosphorylation of downstream proteins, AKT and ERK. Additionally, PPT induced G2/M cell cycle arrest, inhibited the growth of gefitinib-resistant NSCLC cells, and induced apoptosis by suppressing EGFR and MET activity [ 154 ]. These results suggest DPT’s and PPT’s potential as an adjuvant anticancer therapy targeting both EGFR and MET pathways [ 153 , 154 ].…”