Anwuligan inhibits the progression of non‐small cell lung cancer via let‐7c‐3p/PI3K/AKT/mTOR axis

Abstract

Background: Anwuligan (ANW) isolated from nutmeg, also known as myristyl lignan, has attracted attention due to its therapeutic potential in diseases.However, its effect on lung cancer is still unclear. Methods:In this study, the cytotoxicity of ANW on non-small cell lung cancer (NSCLC) cells was detected using a Cell Counting Kit-8 (CCK-8) assay. In vitro, clone formation, wound healing, and Transwell assays were used to investigate the migratory and invasive abilities of NSCLC cells after ANW treatment. The expression levels of the associated proteins were detected using Western blotting. A luciferase assay was used to validate the binding of let-7c-3p to the 3′-untranslated region (UTR) of PIK3CA. In vivo, an A549 cell xenograft mouse model was used to verify the effect of ANW on tumor growth. Results:The results showed that ANW treatment (20 or 50 μM) had obvious cytotoxicity against A549 and H460 cells, suppressing cell proliferation and migration in vitro. In vivo, the growth of the implanted tumor was inhibited by ANW in a nude mouse model. The growth of NSCLC cells was also inhibited by let-7c-3p overexpression in vitro and in vivo. The inhibitory effect of ANW on the proliferation and metastasis of NSCLC cells was weakened by the downregulation of let-7c-3p, whereas it was enhanced by the overexpression of let-7c-3p; PIK3CA was the main target of let-7c-3p. Conclusions:In summary, ANW inhibits the growth and metastasis of NSCLC cells in vivo and in vitro by upregulating the expression of let-7c-3p, which can regulate the PI3K/AKT/mTOR signaling pathway. PIK3CA is the main target of let-7c-3p.

Design, Synthesis and Biological Evaluation of 6-(Imidazo[1,2-a]pyridin-6-yl)quinazoline Derivatives as Anticancer Agents via PI3Kα Inhibition

“…Notably, most of the active compounds were more sensitive to HCC827 cells. In addition to HCC827 cells, PI3K was also overexpressed in other tested cells [ 29 , 30 , 31 , 32 ]. As to the reasons for the different sensitivity of the compounds to these tested cells, we hypothesized it might be because the PI3K pathway is not as equally important in the survival and proliferation of these cells as it is in HCC827 cells.…”

Advances in the role of microRNAs associated with the PI3K/AKT signaling pathway in lung cancer

“…Interestingly, another study found that lidocaine inhibits lung cancer cell growth and metastasis via controlling miR-539, which prevents the signaling pathways ERK and PI3K/AKT from being activated ( 84 ). Anwuligan (ANW) isolated from nutmeg, also known as myristyl lignan, has been found to have therapeutic potential for a variety of diseases, in lung cancer, the latest studies have confirmed that ANW inhibits the growth and metastasis of NSCLC cells by up-regulating the expression of let-7c-3p ( 85 ). Previous studies have confirmed that the reduction of quinone to hydroquinone plays an important role in anti-tumor activity.…”