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

Sun, Pengyan; Qu, Youxing; Wang, Yuna; Wang, Jing; Sheng, Jun

doi:10.7150/jca.54574

Cited by 7 publications

(6 citation statements)

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“…Compound 2 ( wighteone ) was the most active against Pf Dd2 (IC 50 = 11.9 ± 2.4 μM) and Pf 3D7 (IC 50 = 24.6 ± 1.5 μM). However, a recent report indicated that wighteone inhibits cell proliferation, suppressed EGFR signalling pathway, caused cell cycle redistribution and induced cell apoptosis, and could provide a novel potential therapeutic strategy for NSCLC patients with T790M mutation (Sun et al 2021 ). For further consideration of this compound ( 2 ) as starting point for antimalarial drug discovery, cytotoxicity assessment using normal mammalian cells is required.…”

Section: Resultsmentioning

confidence: 99%

Constituents from ripe figs of Ficus vallis-choudae Delile (Moraceae) with antiplasmodial activity

et al. 2022

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Ripe figs, barks, and wood of Ficus vallis-choudae are used in traditional medicine against several conditions including nausea and malaria. However, its use is still to be scientifically documented and validated. Hence, the aim of the present work was to evaluate the antiplasmodial activity of the dichloromethane-methanol (DCM-MeOH (1:1)) crude extract, their hexane, dichloromethane, ethyl acetate, and methanoli fractions, as well as the isolated chemical constituents. The chemical study of the DCM-MeOH (1:1) crude extract of F. vallis-choudae figs led to the isolation of fifteen (15) known compounds identified based on their spectroscopic data [one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR), mass spectrometry] and by comparison of these data with those reported in the literature. Some of the isolated compounds were assessed in vitro for their antiplasmodial activity against Plasmodium falciparum chloroquine-sensitive 3D7 ( Pf 3D7) and multidrug-resistant Dd2 strains. The dichloromethane fraction exhibited very good antiplasmodial activity against both strains with IC 50 values of 13.86 μg/mL and 8.18 μg/mL, respectively. Among the tested compounds, wighteone ( 2 ) was the most active against P. falciparum 3D7 (IC 50 = 24.6 ± 1.5 μM) and Dd2 (IC 50 = 11.9 ± 2.4 μM) strains. The obtained results could justify the traditional uses of F. vallis-choudae against malaria. Wighteone appears to be the most active ingredient. However, further consideration of this compound as starting point for antimalarial drug discovery will depend upon its selectivity of action towards Plasmodium parasites. Highlights • 15 (fifteen) compounds were isolated from the dichloromethane-methanol extract of Ficus vallis-choudae. • Their structures were determined on the basis of their spectroscopic data. • The dichloromethane fraction showed promising activities on the Pf 3D7 and Pf Dd2 strains with IC 50 values of 13.86 and 8.18 µg/mL, respectively. • Wighteone was the most active compound against Pf Dd2 (IC 50 = 11.9 ± 2.4 μM). Graphical abstract Supplementary Information The online version contains supplementary material available at 10.1007/s00436-022-07540-5.

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Section: Resultsmentioning

confidence: 99%

Constituents from ripe figs of Ficus vallis-choudae Delile (Moraceae) with antiplasmodial activity

et al. 2022

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“…Wighteone ( 55 , Figure 9) is a flavonoid in several plants, such as Cudrania cochinchinensis, Erythrina suberosa , and Glycyrrhiza glabra (Sun et al, 2021). 55 exhibited antitumor effects against the Ba/F3 cell line with EGFR L858R/T790M mutation and NCl‐H1975 cell line with IC 50 values of 1.88 and 5.70 μM, respectively.…”

Section: Novel Drug Candidates Obtained From Natural Sources With Egf...mentioning

confidence: 99%

“…55 induced apoptosis, inhibited cell proliferation, suppressed EGFR signaling pathway and caused cell cycle redistribution in both cell lines. In addition, 55 markedly inhibited EGF‐induced EGFR phosphorylation and led to the downregulation of ERK and Akt phosphorylation in a concentration‐dependent manner in NCI‐H1975 cells (Sun et al, 2021).…”

Section: Novel Drug Candidates Obtained From Natural Sources With Egf...mentioning

confidence: 99%

“…I G U R E 8 Illustration depicting the anticancer activity of silibinin through inhibition of EGFR/PI3K/LOX, JAK2/STAT5, and PI3K/Akt downstream signaling pathways.tail to the common cytisine skeleton can increase anti-EGFR/HER2 potency. These compounds exhibited prominently antiproliferative activity against breast cancer cells(Wang, Yin, et al, 2022).Wighteone (55, Figure9) is a flavonoid in several plants, such as Cudrania cochinchinensis, Erythrina suberosa, and Glycyrrhiza glabra(Sun et al, 2021). 55 exhibited antitumor effects against the Ba/F3 cell line with EGFR L858R/T790M mutation and NCl-H1975 cell line with IC 50 values of 1.88 and 5.70 μM, respectively.…”

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confidence: 99%

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Targeting epidermal growth factor receptor and its downstream signaling pathways by natural products: A mechanistic insight

Damare,

Engle,

Kumar

2024

Phytotherapy Research

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The epidermal growth factor receptor (EGFR) is a transmembrane receptor tyrosine kinase (RTK) that maintains normal tissues and cell signaling pathways. EGFR is overactivated and overexpressed in many malignancies, including breast, lung, pancreatic, and kidney. Further, the EGFR gene mutations and protein overexpression activate downstream signaling pathways in cancerous cells, stimulating the growth, survival, resistance to apoptosis, and progression of tumors. Anti‐EGFR therapy is the potential approach for treating malignancies and has demonstrated clinical success in treating specific cancers. The recent report suggests most of the clinically used EGFR tyrosine kinase inhibitors developed resistance to the cancer cells. This perspective provides a brief overview of EGFR and its implications in cancer. We have summarized natural products‐derived anticancer compounds with the mechanistic basis of tumor inhibition via the EGFR pathway. We propose that developing natural lead molecules into new anticancer agents has a bright future after clinical investigation.

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“…Sun et al reported that wighteone ( 101 ) docks at the ATP binding site of EGFR L858R/T790M and forms two hydrogen bonds with the carbonyl group of Gln791 and the amino group of Met793, indicating that it may directly bind to EGFR L858R/T790M. Wighteone has a significant inhibitory effect on Ba/F3 and NCI-H1975 cells expressing EGFR L858R/T790M, with IC 50 values of 1.88 μmol/L and 5.70 μmol/L, respectively [ 200 ] (Fig. 14 ).…”

Section: Egfr-dependent Drug Resistance Mechanismsmentioning

confidence: 99%

Emerging strategies to overcome resistance to third-generation EGFR inhibitors

et al. 2022

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Epidermal growth factor receptor (EGFR), the receptor for members of the epidermal growth factor family, regulates cell proliferation and signal transduction; moreover, EGFR is related to the inhibition of tumor cell proliferation, angiogenesis, invasion, metastasis, and apoptosis. Therefore, EGFR has become an important target for the treatment of cancer, including non-small cell lung cancer, head and neck cancer, breast cancer, glioma, cervical cancer, and bladder cancer. First- to third-generation EGFR inhibitors have shown considerable efficacy and have significantly improved disease prognosis. However, most patients develop drug resistance after treatment. The challenge of overcoming intrinsic and acquired resistance in primary and recurrent cancer mediated by EGFR mutations is thus driving the search for alternative strategies in the design of new therapeutic agents. In view of resistance to third-generation inhibitors, understanding the intricate mechanisms of resistance will offer insight for the development of more advanced targeted therapies. In this review, we discuss the molecular mechanisms of resistance to third-generation EGFR inhibitors and review recent strategies for overcoming resistance, new challenges, and future development directions.

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

Cited by 7 publications

References 35 publications

Constituents from ripe figs of Ficus vallis-choudae Delile (Moraceae) with antiplasmodial activity

Constituents from ripe figs of Ficus vallis-choudae Delile (Moraceae) with antiplasmodial activity

Targeting epidermal growth factor receptor and its downstream signaling pathways by natural products: A mechanistic insight

Emerging strategies to overcome resistance to third-generation EGFR inhibitors

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