Cytotoxicity of Chalcone Derivatives towards Glioblastoma

Background: Among seventeen compounds derived from chalcones investigated as potential anticancer drugs towards LN229 glioblastoma cell line, only two were effective. Materials and Methods: Anticancer activity was investigated by evaluating the cell growth, cell cycle, mitotic index and the cell death. Results: Two compounds, namely C2 and C12, inhibited cell proliferation associated with a blockade in the G 2 /M phase of the cell cycle and arrested the growth of tumour spheroid mimicking in vivo tumour. C2 blocked cells in the G 2 phase whereas C12 blocked cells in the M phase of the cell cycle. C12 and C2 killed 40% and 95% of the cells respectively using complex mechanisms. The two compounds increased the fluorescence of rhodamine-123 and N-acetylcysteine inhibited their activity, suggesting a role for reactive oxygen species in cell death mediated by these two compounds. Conclusion: C2 and C12 are markedly cytostatic and cytolytic to glioblastoma cells and act through different pathways. Glioblastoma represents the most common type of primary tumour of the central nervous system and has a poor prognosis (less than 12 month), requiring a multidisciplinary approach, including surgery, radiotherapy and chemotherapy (1, 2). The classical regimen is radiotherapy and chemotherapy using temozolomide. After disease relapse, some patients can benefit from new schedule, such as inhibitors of topoisomerase I and antiangiogenic in combination, which lead to a moderate increase of survival (3). In this context, the need for new drugs is still highly apparent. For this reason, we investigated the antitumour