A natural product atalantraflavone inhibits non-small cell lung cancer progression via destabilizing Twist1.

Fitoterapia

Department of Thoracic surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou, China. Electronic address:

Published: September 2019

The non-small cell lung cancer (NSCLC) represents a malignant type of cancer worldwide. The atalantraflavone (AFL) is a natural product isolated from leaves of Atalantia monophylla (L.) DC. However, the function of atalantraflavone in NSCLC is still elusive. In present work, we have unraveled a novel function of AFL in NSCLC. AFL significantly inhibited NSCLC cell viability and colony formation. AFL increased sub-G1 fraction and apoptotic rates in a dose-dependent manner. Furthermore, Twist-related protein 1 (Twist1) was identified as the target of AFL. The association between AFL and Twist1 markedly decreased the stability of Twist1 via elevated ubiquitin mediated proteasomal degradation. AFL induced NSCLC suppression was mediated by Twist1 as Twist1 overexpression could partially reverse the inhibitory effect of AFL on migration and metastasis. Furthermore, AFL could also sensitize NSCLC cells to cisplatin treatment and consistently impair NSCLC proliferation and metastasis. Our current data have identified a tumor suppressive function for AFL in NSCLC by increasing Twist1 degradation. Therefore, the anti-tumor activity of AFL might provide critical insight into pharmaceutic lung cancer intervention to overcome cisplatin resistance.

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http://dx.doi.org/10.1016/j.fitote.2019.104275DOI Listing

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