Oxyfadichalcone C inhibits melanoma A375 cell proliferation and metastasis via suppressing PI3K/Akt and MAPK/ERK pathways

Publication date: 1 August 2018Source: Life Sciences, Volume 206Author(s): Xiaolin Peng, Zhengming Wang, Yang Liu, Xin Peng, Yao Liu, Shan Zhu, Zhe Zhang, Yuling Qiu, Meihua Jin, Ran Wang, Qingying Zhang, Dexin KongAbstractAimsMelanoma remains to be one of the most incurable cancers. Discovery of novel antitumor agent for melanoma therapy is expected. We recently isolated Oxyfadichalcone C from Oxytropis falcate and investigated the anti-proliferative and anti-metastatic activity on human melanoma A375 cells in vitro.Main methodsCell viability was determined using MTT assay and soft agar cloning formation assay. The effect of Oxyfadichalcone C on cell cycle distribution and apoptosis were analyzed by flow cytometry. Cell metastasis was determined by wound healing assay, Transwell assay and Gelatin zymography assay. The effect of Oxyfadichalcone C on signal proteins of PI3K/Akt and MAPK/ERK pathways was examined by western blot analysis. Synergism assay was employed to determine whether combination of Oxyfadichalcone C with Vemurafenib would enhance the anti-proliferative effect.Key findingsOxyfadichalcone C potently inhibited proliferation, induced G1 phase arrest and weak apoptosis in A375 cells. Anti-migration and anti-invasion activities were also indicated. Such effects were associated with upregulation of p27, reduction of cyclin D1, p-pRb, p-Integrin β1, as well as the proteolytic activity of metalloproteinase (MMP)-2/9. Meanwhile, key molecules of PI3K/Akt and MAPK/ER...
Source: Life Sciences - Category: Biology Source Type: research