<i>p</i>-Coumaric Acid Inhibits Osteosarcoma Growth by Inhibiting PI3K/Akt Signaling Pathway

Author(s):

Bo Yang, Bowen Wang, Guoliang Wang, Wenliang Cao, Qian Wang, Hao Pu and Wei An*   Pages 1577 - 1586 ( 10 )

Abstract:

Background: <i>P</i>-coumaric acid (p-CA) is a kind of phenylpropionic acid derived from aromatic amino acids, which is widely distributed in many plants and human diets. It has strong pharmacological and inhibitory effects on a variety of tumors. However, the role of <i>p</i>-CA in osteosarcoma, a tumor with a poor prognosis, is still unknown. Therefore, we aimed to evaluate the effect of <i>p</i>-CA on osteosarcoma and explore its potential mechanism. </P> <P> Objective: This study aimed to investigate whether <i>p</i>-CA has an inhibitory effect on the growth of osteosarcoma cells and explore its potential mechanism. </P> <P> Methods: MTT assay and clonogenic assay were used to detect the effect of <i>p</i>-CA on the proliferation of osteosarcoma cells. The effect of <i>p</i>-CA on apoptosis of osteosarcoma cells was detected by the Hoechst staining and flow cytometry. The effects of <i>p</i>-CA on the migration and invasion of osteosarcoma cells were detected by scratch healing assay and Transwell invasion assay. Western blot and PI3K/Akt pathway activator 740Y-P were used to detect the anti-tumor mechanism of <i>p</i>-CA on osteosarcoma cells. The effect of <i>p</i>-CA on osteosarcoma cells in vivo was verified by an orthotopic osteosarcoma tumor animal model in nude mice. </P> <P> Results: MTT assay and clonogenic assay showed that <i>p</i>-CA inhibited the proliferation of osteosarcoma cells. Hoechst stain and flow cytometry showed that <i>p</i>-CA could induce apoptosis of osteosarcoma cells and lead to G2 phase arrest of osteosarcoma cells. Transwell assay and scratch healing assay found that <i>p</i>-CA could inhibit the migration and invasion of osteosarcoma cells. Western blot showed that <i>p</i>-CA could inhibit the activity of the PI3K/Akt signaling pathway in osteosarcoma cells, and 740Y-P could reverse its inhibitory effect. In vivo mouse models, <i>p</i>-CA has an antitumor effect on osteosarcoma cells in vivo, and at the same time, it has less toxic side effects on mice. </P> <P> Conclusion: This study demonstrated that <i>p</i>-CA could effectively inhibit the proliferation, migration and invasion of osteosarcoma cells and promote apoptosis. <i>p</i>-CA may play an anti-osteosarcoma role by inhibiting PI3K/Akt signaling pathway.

Keywords:

p-coumaric acid, osteosarcoma, anti-tumor, PI3K/AKT, phenylpropionic acid, clonogenic assay.

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