Cratoxylumxanthone C, a natural xanthone, inhibits lung cancer proliferation and metastasis by regulating STAT3 and FAK signal pathways

Abstract

To discover phytochemicals as lead compounds for cancer treatment, cratoxylumxanthone C, a natural xanthone, was obtained from Cratoxylum cochinchinense (Lour.) Bl., for which there have been no reports on the biological effects against cancer. Our study revealed that cratoxylumxanthone C had significant anti-tumor activity by inducing apoptosis, augmenting cellular reactive oxygen species (ROS), and arresting cell circle. The mechanistic examination showed the inhibition of A549 cell proliferation and metastasis by cratoxylumxanthone C was coupled with the signal transducer and activator of transcription 3 (STAT3) and focal adhesion kinase (FAK) signaling pathways. Furthermore, the zebrafish models confirmed its significant in vivo anti-tumor activity, in which cratoxylumxanthone C inhibited tumor proliferation and metastasis and suppressed the angiogenesis. Comprehensively, these cellular and zebrafish experiments implied that cratoxylumxanthone C may have the potential to become an anti-tumor agent for lung cancer, especially non-small cell lung cancer (NSCLC).

The Lung Adenocarcinoma Microenvironment Mining and Its Prognostic Merit

“…[19][20][21][22] It has been found in lung cancer cells that the upregulation of ARHGAP15 can inhibit cell proliferation, migration and invasion by reducing the expression of vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP2), MMP9, and the phosphorylation of signal transducer and activator of transcription-3 (p-STAT3). 23 B and T lymphocyte associated (BTLA) plays a crucial role in the transmission of immunosuppressive signals. 24,25 It has been found to increase the expression of CD4(þ) and CD8(þ) T cells in the pleural fluid of patients with lung cancer and can downregulate the expression of the T cell activation marker CD25 to inhibit the production of inflammatory cytokines.…”

Dietary Polyphenols Effects on Focal Adhesion Plaques and Metalloproteinases in Cancer Invasiveness

“…An overall reduction in the expression of MMP-2 and MMP-9 was also observed by Luo and his team upon treatment of glioma cells with gartaninin [ 249 ]. An inhibition of cell migration and a downregulation of the FAK/MMP-dependent signaling pathway were observed after treatment with cratoxylumxanthone C in A549 lung cancer cells (7.5–30 μM) [ 250 ].…”

Application of Zebrafish as a Model for Anti-Cancer Activity Evaluation and Toxicity Testing of Natural Products

“…Like xipsxanthone H ( 7 ), another xanthone compound, cratoxylumxanthone C ( 10 ) isolated from Cratoxylum cochinchinense (Lour.) Blume, also exhibited anti-angiogenic effects in the Tg (fli1: EGFP) transgenic zebrafish model [ 47 ]. In this study, Li et al, (2022) found that the ISVs’ length of the zebrafish decreased from 2560 to 1586 µm with increasing concentrations of cratoxylumxanthone C (5, 10, and 20 µM), indicating that cratoxylumxanthone C had a blockage effect on the blood vessels of zebrafish.…”

“… - ISVs, DLAVs, DA. - 24 hpf 2022 [ 47 ] Cratoxylumxanthone C ( 10 ) Cratoxylum cochinchinense (Lour.) Blume - ISVs Sunitinib malate 54 hpf 2020 [ 48 ] Eupatilin ( 11 ) Artemisia asiatica Nakai ex Pamp.…”

“…Additionally, Li et al, (2022) found that cratoxylumxanthone C ( 10 ) isolated from C. cochinchinense possessed significant anti-cancer activity on non-small cell lung cancer using a zebrafish xenograft model [ 47 ]. They labeled A549 cells with CM-Dil dye, and then microinjected the cells into the yolk sac of zebrafish embryos.…”