
Marine toxin (+)‐chaetocin‐induced apoptosis of lung large cell carcinoma cell lines through cell cycle arrest via CDKN1A expression and replicative stress
Author(s) -
Qian Mengjia,
Cao Xin
Publication year - 2022
Publication title -
clinical and translational discovery
Language(s) - English
Resource type - Journals
ISSN - 2768-0622
DOI - 10.1002/ctd2.49
Subject(s) - apoptosis , cell cycle checkpoint , cancer research , cell , cell cycle , programmed cell death , cell growth , cell culture , biology , lung cancer , lung , carcinoma , chemistry , microbiology and biotechnology , medicine , biochemistry , genetics
Abstract Lung large cell carcinoma is a common type of lung cancer with poor prognosis. Although targeted drugs have achieved enormous success in treating non‐small‐cell lung carcinoma (NSCLC), new chemotherapy is needed since the emerged drug resistance always hinders curative effects. The fungal toxin (+)‐chaetocin demonstrated strong antineoplastic activities against the tested lung large cell carcinoma cell lines H460 and H661 at submicromolar concentrations. Further research demonstrated that (+)‐chaetocin effectively induced H460 apoptosis at 10–30 nM concentrations, while cell death occurred at 60 nM concentrations due to DNA duplication errors. Cell cycle and transcriptional analyses proved that cell cycle arrest via CDKN1A expression and the comprehensive replicative stress of (+)‐chaetocin are key factors in the (+)‐chaetocin working mechanisms.