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

Yeling Li; Huimei Wang; Wenhui Liu; Jiantong Hou; Jing Xu; Yuanqiang Guo; Ping Hu

doi:10.3389/fphar.2022.920422

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

Front Pharmacol. 2022 Aug 9:13:920422. doi: 10.3389/fphar.2022.920422. eCollection 2022.

Authors

Yeling Li¹, Huimei Wang¹, Wenhui Liu¹, Jiantong Hou¹, Jing Xu¹, Yuanqiang Guo^{1

2}, Ping Hu³

Affiliations

¹ State Key Laboratory of Medicinal Chemistry Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, China.
² Key Laboratory of Tropical Medicinal Resource Chemistry of Ministry of Education, Hainan Normal University, Haikou, China.
³ Key Laboratory of Research on Pathogenesis of Allergen Provoked Allergic Disease in Liaoning Province, Shenyang Medical College, Shenyang, China.

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).

Keywords: FAK; anti-tumor; cratoxylumxanthone C; natural xanthone; stat3; zebrafish.