Study On The Anti - Cancer Effect And Mechanism Of Malachite Green In Oral Cancer And Lung Cancer Cell Line

BackgroundMalachite green chloride (MG) is widely used in dye industry and aquaculture. Due to its potential carcinogenic effects, MG has never been explored for medical applications. In screening drug repurpose libraries, MG was found potent against an oral cancer cell line. The purpose of this study was to determine the anti-cancer activity of MG and mechanisms of the action.MethodA serial concentrations of MG were applied to 5 lung and 2 oral cancer cell lines and the effect was measured using MTT (3-(4,5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay 24 h after adding MG. Flow cytometry was used to determine the cell cycle distributions before and after MG treatment. Western blot analysis was used to determine status of key proteins critical for cell proliferation and apoptosis. A xenograft lung cancer model was used to test MG’s anti-cancer effectin vivo.ResultMG has a strong anti-cancer effect with half maximal inhibitory concentration (IC50) ranging from 0.1 to 0.6 μM for the tested cancer cell lines. MG treatment resulted in substantially increased cells in sub-Gl% phase and increased PARP cleavagein all cancer cell lines tested except A549. For A549 cells, MG resulted in Gl cell cycle arrest but such arrest accompanied with a surprising down-regulation of retinoblastoma (Rb) protein level and increased Cyclin E2 level. In the xenograft model inoculated with A549 cells, MG treatment inhibited tumor growth.ConclusionMG possesses an anti-cancer activity through inducing apoptosis or Rb-independent G1 arrest in lung and oral cancer cells. Further studies to explore MG as an anti-cancer agent are warranted.