Psorachromene induces apoptosis and suppresses tumor growth in NSCLC cells harboring EGFR L858R/T790M/C797S

Tong-Hong Wang; Yann-Lii Leu; Chin-Chuan Chen; Hsin-Jung Li; Shuenn-Chen Yang; Kuo-Yen Huang; Chi-Yuan Chen

doi:10.1002/ptr.7432

Psorachromene induces apoptosis and suppresses tumor growth in NSCLC cells harboring EGFR L858R/T790M/C797S

Phytother Res. 2022 May;36(5):2116-2126. doi: 10.1002/ptr.7432. Epub 2022 Mar 1.

Authors

Tong-Hong Wang^{1

2}, Yann-Lii Leu^{2

3}, Chin-Chuan Chen^{2

3}, Hsin-Jung Li⁴, Shuenn-Chen Yang⁵, Kuo-Yen Huang^{6

7}, Chi-Yuan Chen^{1

2}

Affiliations

¹ Graduate Institute of Health Industry Technology and Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan.
² Tissue Bank, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
³ Graduate Institute of Natural Products, Chang Gung University, Taoyuan, Taiwan.
⁴ Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan.
⁵ Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
⁶ Department and Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan.
⁷ National Taiwan University YongLin Institute of Health, National Taiwan University, Taipei, Taiwan.

PMID: 35229911
DOI: 10.1002/ptr.7432

Abstract

The extracts from Psoralea corylifolia Linn. (P. corylifolia) seeds have been shown to display antitumor activity. To date, the prospects of this plant and its active compounds in the treatment of non-small-cell lung cancer (NSCLC) have not been thoroughly studied. In this study, we identified a novel psorachromene compound that displays selective cytotoxic effects on all NSCLC cells tested, including NSCLC cells harboring epidermal growth factor receptor (EGFR) activation mutants (H1975^L858R/T790M and H1975-MS35^{L858R/T790M/C797S} ). Psorachromene induces G1 arrest in NSCLC cells harboring wild-type EGFR but induces apoptosis in NSCLC cells harboring activating EGFR mutations. Psorachromene inhibits activated EGFR signaling and kinase activity and suppresses tumor growth of implanted H1975-MS35^{L858R/T790M/C797S} cells in nude mice. Molecular docking analysis revealed that psorachromene could form stronger bonds with mutant EGFR than wild-type EGFR, which might account for the greater cytotoxic effects observed in NSCLC cells harboring activating EGFR mutations (H1975 and H1975-MS35) than wild-type EGFR (A549). In conclusion, it is suggested that psorachromene is an attractive agent to be further explored for its use in the treatment of NSCLC patients harboring EGFR L858R/T790M/C797S.

Keywords: EGFR; Psoralea corylifolia; drug resistance; lung cancer; psorachromene.

MeSH terms

Animals
Antineoplastic Agents* / pharmacology
Antineoplastic Agents* / therapeutic use
Apoptosis
Carcinoma, Non-Small-Cell Lung* / drug therapy
Carcinoma, Non-Small-Cell Lung* / genetics
Carcinoma, Non-Small-Cell Lung* / pathology
Cell Line, Tumor
ErbB Receptors / genetics
Humans
Lung Neoplasms* / drug therapy
Lung Neoplasms* / genetics
Lung Neoplasms* / pathology
Mice
Mice, Nude
Molecular Docking Simulation
Mutation
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / pharmacology
Protein Kinase Inhibitors / therapeutic use

Substances

Antineoplastic Agents
Protein Kinase Inhibitors
EGFR protein, human
ErbB Receptors

Abstract

MeSH terms

Substances

Grants and funding